Inbred strains of mice, rats and guinea-pigs have been available for nearly a century. And yet many research workers do not fully understand their properties and value in research. This page reviews the history of their introduction into biomedical research.
Early Years
Inbreeding of guinea-pigs, rats and mice
The Jackson Laboratory
Immunogenetics
Literature and communication
More Recent Developments
References
Early Years
Mendel’s laws
The rediscovery of Mendel’s 1866 paper in 1900 by De Vries, Correns and Tschermak conveniently marks the beginning of modern genetics. This led to controversy about the importance of Mendelian genetics in evolution. The “Mendelians”, led by William Bateson, thought that the laws would prove to be universal while the “Biometricians”, led by Karl Pearson were unable to reconcile Mendel’s laws with the inheritance of quantitative characteristics (Provine 1971). Inbred strains were unknown at this time in mammals, although they occur naturally in self-fertilising plants, but Mendel’s laws showed immediately that “pure” (i.e. homozygous) lines breed true, an important attribute of inbred strains.
Self-fertilised beans
In 1903 Johannsen, who worked with self-fertilised beans published a paper on “Heredity in populations and pure lines”; the first paper to demonstrate the properties of inbred strains. He recognised that his material could be divided up into pure lines, i.e. it consisted of parallel sub-strains of inbred strains. Selection was found to be effective in altering the mean, but it arose from “. . . a step-wise progression in each generation of the differing lines concerned”. Similarly, when the material was considered as a whole (i.e. including all the substrains), Galton’s law of regression to the mean was found to be fully substantiated. However, when considering individual pure lines, he found that: “It has been demonstrated that in all cases within the pure lines the retrogression mentioned above has been completed. Selection within pure lines has produced no new shift in the genotype.” (Peters 1959). Selection within modern inbred strains of laboratory animals is similarly ineffective in changing their characteristics (Ginsburg 1967).
First transplantable tumours
Hints of the potential value of inbred strains of mice in cancer research came between 1902 and 1908. Early attempts to transplant tumours led to unpredictable results: in some cases the tumours survived, but in others they did not, and the reasons for this were not known (Klein 1975). However, a spontaneous alveolar carcinoma was successfully propagated through 19 generations using a single stock of “white mice” which had apparently become relatively inbred through being maintained as a closed population for many years (Jensen 1903). Transplantation of the tumour to other stocks of mice failed. Similarly, a tumour of Japanese waltzing mice was successfully grown in other mice of the same stock (Loeb 1908). These waltzing mice had been bred in the Far East for many centuries, where it was known that the waltzing characteristic was recessive; hence, the mice were probably highly inbred.
The genetic basis of tumour rejection
The work of Jensen and Loeb led to the recognition of the importance of “race” as a factor governing susceptibility to transplantable tumours, and the suggestion that susceptibility to such tumours may be inherited. An explanation of the genetic basis of tumour rejection was developed by Little in 1914. He showed that the pattern of susceptibility could be explained on the basis of acceptance being dependent on a number of genes acting with a dominant mode of inheritance (Klein 1975). Eventually, studies of the nature of these genes contributed substantially to the development of a whole new branch of immunology, the study of the histocompatibility genes and the cell mediated immune response.
Inbreeding of mice, rats and guinea-pigs
Inbreeding of guinea-pigs
In 1906 an inbreeding experiment involving guinea-pigs was started by G. M. Rommel of the Animal Husbandry Division of the United States Department of Agriculture. Strain 2 and 13 guinea-pigs, derived from these are still in use today. The experiment was taken over in 1915 by Dr Sewall Wright. “Faced with the task of analysing the accumulated data he (Wright) became seriously interested in constructing a general mathematical theory of inbreeding”. (Provine 1971). By 1920 Wright had developed his method of path coefficients, which he then used to develop his mathematical theory of inbreeding. He introduced the inbreeding coefficient F as the correlation between uniting gametes in 1922, and most of the subsequent theory of inbreeding has been developed from his work. The definition of the inbreeding coefficient now most widely used is mathematically equivalent to that of Wright (Falconer 1981).
Inbreeding of rats and mice
The period before World War I also led to the initiation of inbreeding in rats by Dr Helen King in about 1909 (King 1918) and in mice by Dr C. C. Little in 1909 (Staats 1966). The latter project led to the development of the DBA strain of mice, now widely distributed as the two major substrains DBA/1 and DBA/2, which were separated in 1929-1930. DBA mice were nearly lost in 1918, when the main stocks were wiped out by murine paratyphoid, and only three un-pedigreed mice remained alive (Strong 1942). Soon after World War I, inbreeding in mice was started on a much larger scale by Dr L. C. Strong, leading in particular to the development of strains C3H and CBA, and by Dr C. C. Little, leading to the C57 family of strains (C57BL, C57BR and C57L). Many of the most popular strains of mice were developed during the next decade, and some are closely related. Evidence from the uniformity of mitochondrian DNA suggests that most of the common inbred mouse strains were probably derived from a single breeding female about 150-200 years ago (Ferris et al 1982).
A chart of the genealogy of mouse inbred strains is maintained on the Jackson Laboratory web site.
Many of the most widely used inbred strains of rats were also developed during this period, several of them by Curtis and Dunning at the Columbia University Institute for Cancer Research (Curtis et al 1931). Strains dating back to this time include F344, M520 and Z61 (in 1920) and later ACI, ACH, A7322 and COP. Tryon’s classic work on selection for maze-bright and dull rats led to the development of the TMB and TMD inbred strains, and later to the common use of inbred rats by experimental psychologists.
The Jackson Laboratory
Founding
The founding of the Roscoe B. Jackson Memorial Laboratory (now The Jackson Laboratory) at Bar Harbor, Maine, in 1929 by Dr C. C. Little was an event of great importance in the history of inbred strains. According to E. L. Green, who succeeded Dr Little as Director in 1956: “The purpose of The Jackson Laboratory is to increase man’s knowledge of himself, of his development, growth and reproduction, of his physiological and psychological behaviour, and of his inborn ailments, through research with genetically controlled experimental animals” (Green 1966).
Early work
The earliest investigations were a reflection of the research interests of Dr Little in the genetics of cancer and in radiation biology. “Underlying these two predominant types of study was a continuing effort to improve the “tools” (Green 1966). This meant the continuing development of inbred strains of mice each with its unique set of distinguishing characteristics, the discovery and propagation of new mutations, and the development of more and more basic knowledge of the early embryogenesis, histogenesis, growth, pathogenesis, teratogenesis, ageing patterns, normal and abnormal physiology, and reproductive behaviours of the increased number of strains. In the exact characterisation and analysis of the differences between the inbred strains, and between mutant and non-mutant types within an inbred strain, lay the research ore to be mined.
The staff of the Jackson Laboratory soon began to make a significant contribution to research. An early discovery published in 1933 was that mammary tumours in mice arose as a result of an “agent” which was passed from mother to offspring through the milk. This could be eliminated if the young were fostered onto a low mammary tumour strain, suggesting that these tumours were caused by a vertically transmitted virus. The Laboratory has continued to play a leading role in cancer research, immunology, genetics and many other areas of research involving the mouse as a model organism (see below).
Training
In addition to its role as a research institute, The Jackson Laboratory has played an important part in training research scientists. Training programmes range from short courses on mammalian and medical genetics to programmes for high school students, and pre- and post-doctoral appointments. Established research workers have also been encouraged to come to Bar Harbor to carry out short projects in collaboration with staff scientists. As a result of these various training programmes, many research scientists have come to realise the value of using genetically defined stocks in their research programmes. This influence was also extended by the publication of The Biology of the Laboratory Mouse, edited by G. D. Snell, in 1941, with a second edition, edited by E. L. Green, in 1966.
Supply of animals
The Jackson Laboratory has always been a supplier of animals. “From its earliest days the Laboratory has followed a policy of making any research materials it can spare available to research workers elsewhere.” (Green 1966). The Laboratory now has the largest collection of mouse genetic stocks in the world. Sales of animals make a substantial contribution to the total budget. The work of the Laboratory was interrupted in 1947 when it was destroyed by fire. However, most of the stocks were eventually recovered from other investigators. A second fire in May 1989 led to the loss of a large breeding facility and several thousand mice, but no strains were lost. Breeding colonies of all commercial strains are now always maintained on more than one site.
Immunogenetics
The alloantigen hypothesis
In 1933 Haldane proposed the alloantigen hypothesis of tumour regression (Haldane 1933). The genetic theory of transplantation developed by Little and Tyzzer (Klein 1975) failed to define the nature of the hypothetical susceptibility genes. By this time it was generally believed that neoplastic cells differed from normal cells and that there was an immune reaction directed against this difference. However, this did not explain why tumours were not rejected when transplanted within an inbred strain. Haldane postulated that an immunity was directed against alloantigens, rather than tumour-specific antigens. He predicted that antigenic differences similar to blood group differences exist in other tissues and that a tumour arising in a tissue preserves the alloantigen characteristics of that tissue. He further speculated that the tumour alloantigens induce an immune response in a host lacking them. Transplantation within an inbred strain does not induce such a response because the donor of the tumour and the host share the same antigens.
In 1936 Peter A. Gorer, working at the Lister Institute, London, discovered four blood group antigens in the mouse, which he designated I, II, III and IV (Klein 1975). In 1937 he showed that one of these, antigen II, was associated with resistance to transplanted tumours. Gorer’s work demonstrated that the genes for susceptibility to tumour transplants were identical with the genes coding for alloantigens, and also conclusively demonstrated the immunological basis of tumour rejection. The antigen II locus later became known as the H-2 locus or H-2 complex (now designated H2; hyphens were eliminated from gene symbols in 1994).
Further work on genetics of tumour rejection
The next major step was the further analysis of the genetic basis of tumour rejection by G. D. Snell, at The Jackson Laboratory, who recognised that the first step in the analysis was to separate and identify individual histocompatibility loci and alleles. This was achieved by backcrossing from a donor stock to an inbred strain with appropriate selection, and the resultant lines were called initially coisogenic and later congenic lines (Snell 1948). In any pair of congenic lines of this type, one of the lines resists tumour grafts from the other line, so they are also called congenic resistant lines. Such mouse and rat lines are now widely used in immunological research. By using congenic lines has it become possible to dissect out and study the various loci governing the cell-mediated immune response, work for which George Snell was a co-recipient of the 1980 Nobel Prize in Physiology and Medicine. Moreover, the use of congenic lines in immunology has demonstrated their potential value in other fields. It has now become standard practice to study mutants and transgenes only when they are maintained as a congenic line on an inbred strain genetic background.
Literature And communication
Problems with accumulating information
By the beginning of World War II there were large numbers of inbred strains and mutants of mice, and genetic nomenclature and the flow of information between investigators in Europe and the USA was beginning to be a problem. Accordingly, in 1939 a letter was circulated by George Snell asking whether a Committee on Mouse Genetic Nomenclature should be formed. This letter was favourably received, and a small committee consisting of Drs Crew (later replaced by Gruneberg), Dunn and Snell was formed. Proposals for a system of genetic nomenclature were canvassed, and after much discussion and a ballot the resulting rules were published in the Journal of Heredity in 1940. The accompanying gene list included a total of 31 genetic loci. The committee (with a new and enlarged membership) continues to ensure that nomenclature systems are adequate to cope with genetic advances, and publishes new rules where appropriate. Rules for chromosome nomenclature were also formulated (Committee on Standardised Nomenclature of Mice 1972).
More recently, the rules have undergone a process of almost constant review as new types of genetic marker such as gene and DNA probes have been developed. Gene symbols are also being changed as the biochemical processes underlying a mutation are elucidated, and in an attempt to keep common nomenclature for the same genes in different species, including humans.
Brief nomenclature rules for inbred strains are given elsewhere in this web site (see Nomenclature button), with more extensive rules both for inbred strains and genes given on the Jackson Laboratory web site.
Early sources of information
The first edition of Biology of the Laboratory Mouse, published in 1941(Snell 1941), and edited by Dr G. D. Snell, helped to consolidate information available at that time. Chapters included early embryology, histology, spontaneous neoplasma, gene and chromosome mutations, the genetics of spontaneous tumour formation, the genetics of tumour transplantation, endocrine secretion and tumour formation, the milk influence in tumour formation, inbred and hybrid animals and their value in research, parasites, infectious diseases of mice and care and recording. Most of the references to inbred strains occurred in the chapters on various aspects of cancer and are now largely out of date, although the chapter on the value of inbred strains and hybrids by W. L. Russell was one of the first written statements on the value of inbred strains in research and remains valid to this day. The second edition of Biology of the Laboratory Mouse, edited by E. L. Green, was published in 1966 (Green 1966), with individual chapters written by staff of The Jackson Laboratory. This book covered all aspects of mouse biology and again led to the consolidation of information available up to that time.
The Genetics of the Mouse, by Hans Gruneberg, published in 1943, with a second edition in 1952, (Gruneberg 1952) summarised the information to date on genetic variation in the mouse. Although the book did not deal specifically with inbred strains, it gave many examples of the differences between strains both in anatomical features and resistance to disease. Genetic variants and strains of the laboratory mouse, edited by Dr. Margaret Green in 1989, with a second edition edited by Drs. Mary Lyon and A.G. Searle in 1989, and a 3rd. edition published in 1996, edited by Drs. Mary Lyon Sohaila Rastan and SDM Brown (Lyon et al 1996) is essentially it is a catologue of information on mouse genetics. However, there is so much information and it is up-dated so frequently that it is now only manageable on the Web. “Mouse Genetics” by Lee Silver (Silver 1995) is a true successor to Gruneberg’s book. It covers the history and origins of laboratory mice, the mouse genome, mutagenesis and transgenesis, genetic mapping and linkage analysis and other strategies for locating genes.
Mouse News Letter
In 1939 George Snell had also foreseen the need to improve communications between geneticists working with the mouse, and proposed that a Mouse Genetic News should be produced. The first edition was published in November 1941, but because of the war it could only be distributed in North America. It contained the rules on gene nomenclature, lists of mutants and inbred strains, and lists of laboratories holding mouse stocks. A second edition was published in the Journal of Heredity in 1948. Although this publication was useful, it was recognised by many that a regular news sheet was needed. Eventually, Mouse News Letter was started, and the first edition was produced in July 1949, under the editorship of Drs L. C. Dunn and S. Gluecksohn-Schoenheimer, although the editorship was immediately handed over to Dr T. C. Carter. By 1958 Mouse News Letter (MNL) was being edited by Dr Mary Lyon, who stated its functions as follows:
1. “The reporting of new mutants, inbred strains and substrain symbols, and the ancillary function of helping contributors in standardising symbols and avoiding duplication.
2. The locating of stocks of mutants and inbred strains.
3. The prevention of loss of important stocks by enabling contributors to advertise their intention to discontinue these stocks.
4. The dissemination of general news of interest to mouse workers (those items at the front of MNL).
5. The notification of research news.”
According to Dr. Lyon “MNL is not a journal for the publication of scientific results. The research items are intended to indicate to readers what subjects are under investigation (Work in progress) and what published results they may expect to find in other periodicals either now (Publications) or in the future (Research notes).’
In 1990 Mouse News Letter changed its name to Mouse Genome, in order to reflect the ever increasing emphasis on fundamental mouse genetics. It also began to accept short refereed reports in addition to the unrefereed Laboratory Reports, and increased publication to four times per year. Finally, it was incorporated into a more formal journal Mammalian Genome.
In 1954 a new dimension was added to Mouse News Letter with the publication of the first bibliography listing of inbred strains by Joan Staats. This contained about 270 references to papers which had used inbred or mutant mice, published during six months of 1953 and indicating which strains were used in each study. Some 46 per cent of the papers were from the general area of cancer research, with less than 4 per cent being in the field of immunology. This bibliographical supplement continued until Joan Staats retired in 1984.
First listing of inbred strains of mice
The Committee on Standardised Nomenclature for Inbred Strains of Mice, published its first report in 1952. It included rules for the nomenclature of inbred strains, the first listing of more than 80 such strains and a list of those people or institutions which maintained them. Examination of the long lists of synonyms for some of these strains shows that by this time nomenclature had almost got out of hand, and it took a number of subsequent editions to get the listings into good order.
The first listing of inbred strains of other species was published (Billingham and Silvers 1959), but lack of a committee on nomenclature or appropriate News Letters for other species has resulted in continuing confusion, although the lists of strains of rats was updated in 1990 before it was eventually transferred to the Web (Greenhouse et al 1990).
More Recent Developments
Recombinant inbred strains (1971)
The development of the first set of recombinant inbred strains by D.W. Bailey (Bailey 1971) and their subsequent development on a large scale by B. A. Taylor (both of the Jackson Laboratory) provided research workers with a powerful new tool for genetic analysis of differences between pairs of inbred strains. Sets of RI strains are developed by crossing two standard inbred strains, and then sib mating the offspring for 20 or more generations as a number of parallel “recombinant” strains in which genes from the two parental strains have become assorted into new combinations. Study of the “strain distribution pattern” or “SDP” will often indicate whether or not the observed character is due to the segregation of a single Mendelian locus. If so, there is a strong chance that the pattern may coincide with the pattern observed for a marker locus, which implies genetic linkage. Sets of RI strains can be sometimes be used to map quantitative trait loci (QTLs), although large numbers of strains are needed to resolve more than two or three loci. For example, the AXB, BXA set of RI strains has been used to show that there is a locus for lung tumour susceptibility on chromosome 6 in mice(Malkinson et al 1985). RI strains are particularly useful for analysing characters such a percent mortality which can not be studied in a single individual.
Recombinant congenic strains
“Recombinant congenic strains” (RC) are produced by crossing two standard inbred strains, followed by a few (often 2-4) generations of backcrossing to one of the parental strains, then sib mating (Demant and Hart 1986). These provide an interesting tool for identifying genes associated with polygenic inheritance. The use of these strains is discussed in more detail in chapter 10. More recently, the availability of genetic markers covering the full length of all of the chromosomes has made it possible to develop consomic or chromosome substitution strains in which a whole chromosome from one strain has been backcrossed into another strain(Nadeau et al 2000). A comparison of the background strain with the consomic strain provides a highly sensitive way of determining whether there are any genes on the substituted chromosome which affect the expression of a character of interest. Several sets of such strains are now in development.
Freeze preservation of embryos
The development of a practical technique for the freeze preservation of pre-implantation mouse embryos (Whittingham et al 1972) makes it more economic to preserve strains and congenic lines which are only infrequently used, reduces genetic drift in inbred strains due to the accumulation of new mutations, makes the international exchange of genetic stocks easier, and acts as an insurance against disease or other catastrophe destroying the stocks held at one centre. Although this technique has been available for over thirty years, and is used routinely in some laboratories, there is still considerable scope for its more widespread use. Many laboratories are producing genetically modified mice leading to a proliferation of strains. Embryo freezing can be used as a cost effective way of maintaining stocks which are likely to be wanted in the future, but are not under immediate investigation.
Molecular techniques
Undoubtedly the most significant advance during the last two decades is the exploitation of molecular techniques in biomedical research. The discovery of “variable number of tandem repeas” or VNTR loci by Alec Jeffreys and others (Jeffreys et al 1987) leading to DNA fingerprinting, and the development of genetic markers based on restriction fragment length polymorphisms were important developments. This was followed by the discovery of microsatellite markers which can be detected with very small samples of DNA using the polymerase chain reaction and synthetic oligonucleotide primers (Dietrich et al 1992,Love et al 1990) and the more recent development of methods for detecting single nucleotide polymorphisms (SNPs) has transformed mammalian genetics.{Wiltshire, 2003 959 /id}. For the first time, it is now practical to map quantitative trait loci (QTLs) controlling characters such as susceptibility to tumours and behaviour, although the identification of the individual loci remains a difficult problem. This is discussed in greater detail in later chapters.
Transgenic strains
Transgenic strains (Gordon et al 1980) which carry a foreign stretch of DNA as a result of microinjection into early embryos, have been used in many ways including the study the role of non-coding regions in regulating gene expression, the effects of over-expression of a gene or expression in an abnormal site and the expression of abnormal genes such as oncogenes. Foreign proteins can be produced in, say, milk as a practical method of manufacturing proteins of pharmaceutical importance. About 10% of such strains result in “insertional mutagenesis” when the foreign DNA gets incorporated into the host DNA in such a way that one of the host genes is inactivated. Most transgenic strains are produced using F1 hybrid embryos, as these are more robust than inbred ones. As a result, many genes will segregate in later generations, so the transgenic strain is not inbred. However, it is possible to use inbred embryos of some of the more robust strains. Strain FVB has proved to be of particular value as the male pronucleus, into which DNA is injected, is particularly large and easy to see (Taketo et al 1991). The most widely used embryonal stem cell lines are based on strain 129, so in this case there is the potential to maintain the transgenic strain on an inbred genetic background, although this strain has a poor breeding performance.
Embryonic step cells, “knockout” and related technologies.
ES cells are developed from pre-implantation embryos, and retain the ability to differentiate into all tissue types (i.e. they are “totipotent”). Their development (Evans and Kaufman 1981) was of critical importance in the production of “knockout” mice in which a specific gene is inactivated following homologous recombination with an inactivated gene (Thomas and Capecchi 1987,Travis 1992). The technique is ideal for producing animal models of human diseases such as cystic fibrosis, and hereditary anaemias. It has also been used to study the function of several genes associated with the immune system and cancer, often with surprising results. For example the p53 protein is thought to be a key regulator of cell division, and it was predicted that if the gene for this protein was inactivated, the mice would die soon after birth. However, p53 knockout mice proved to be fully viable, though they do develop a high incidence of tumours from about six months of age (Donehower et al 1992). Many genes can be inactivated without any obvious change in the phenotype. This may be because there are alternative pathways or because the gene only has survival value in some circumstances, such as when encountering a pathogen.
The sequencing of the human genome in 2001 (Lander et al 2001) the mouse in 2002 (Waterston et al 2002) and rat in 2004 will undoubtedly speed up the rate of biological research. The challenge will now be to identify all the genes and their products, and inbred strains of mice are likely to play an important part in this research.
References
Bailey DW (1971), Recombinant inbred strains, an aid to finding identity, linkage, and function of histocompatibility and other genes, Transplantation 11: 325-327
Billingham RE, Silvers WK (1959), Inbred animals and tissue transplantation immunity, Transplantation Bulletin 6: 399-40
Committee (The) on Standardised Nomenclature for Inbred Strains of Mice (1952), Standardised nomenclature for inbred strains of mice, Cancer Research 12: 602-613
Committee on Standardised Nomenclature of Mice (1972), Standard karyotype of the mouse Mus musculus, Journal of Heredity 63: 69-72
Curtis MR, Bullock FD, Dunning WF (1931), A statistical study of the occurrence of spontaneous tumours in a large colony of rats, American Journal of Cancer 15: 67
Demant P, Hart AAM (1986), Recombinant congenic strains- a new tool for analyzing genetic traits determined by more than one gene, Immunogenetics 24: 416-422
Dietrich W, Katz H, Lincoln SE, Shin HS, Friedman J, Dracopoli NC, Lander E (1992), A genetic map of the mouse suitable for typing intraspecific crosses, Genetics 131: 423-447
Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery Jr CA, Butel JS, Bradley A (1992), Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours, Nature 356: 215-221
Evans MF, Kaufman MH (1981), Establishment in culture of pluripotential cells from mouse embryos, Nature 292: 154-156
Falconer DS (1981), Introduction to quantitative genetics, Longman, London, New York
Ferris SD, Sage RD, Wilson AC (1982), Evidence from mt D.N.A. sequences that common strains of inbred mice are descended from a single female, Nature 295: 163-165
Ginsburg BE (1967), Genetic parameters in behavior research, in Behavior genetic analysis, ed. Hirsch J, McGraw-Hill, New York p 135-153
Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH (1980), Genetic transformation of mouse embryos by microinjection of purified DNA, Proceedings of the National Academy of Sciences 77: 7380-7384
Green EL (1966), Biology of the laboratory mouse, McGraw-Hill, New York
Greenhouse DD, Festing MFW, Hasan S, Cohen AL (1990), Catalog of inbred strains of rats, in Genetic monitoring of inbred rat strains, ed. Hedrich H, Gustav Fischer Verlag, Stuttgart, New York p 410-480
Gruneberg H (1952), The Genetics of the Mouse, Nijhof, The Hague p 1-650
Haldane JBS (1933), The genetics of cancer, Nature 132: 265-267
Jeffreys AJ, Wilson V, Kelly R, Taylor BA, Bulfield G (1987), Mouse DNA ‘fingerprints’: analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains, Nucleic Acids Research 15: 2823-2836
Jensen CO (1903), Experimentelle untersuchungen uber krebs bei mausen, Zentralbl.Bakteriol.Parasitenk Infektions-Xrankh. 34: 28-34, 122
King HD (1918), Studies on inbreeding. 1. The effects of inbreeding on the growth and variability in the body weight of the albino rat, Journal of Experimental Zoology 26: 1-54
Klein J (1975), Biology of the mouse histocompatibility-2 complex, Springer-Verlag, Berlin
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la BM, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, Szustakowki J, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S (2001), Initial sequencing and analysis of the human genome, Nature 409: 860-921
Leucotte G (1975), Depression consenguine et modele a dopuble seuil chez la Caille domestique ({ICoturnix coturnix japonica}), Experimentation Animale (France) 8: 201-208
Loeb L (1908), Å¡ber enstehung eines Sarkoms nach Transplantation eines Adenocarcinoms einer japanischen maus, Z.Krebsforsch. 7: 80-110
Love JM, Knight AM, McAleer MA, Todd JA (1990), Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites, Nucleic Acids Research 18: 4123-4130
Lyon MF, Rastan S, Brown SDM (1996), Genetic variants and strains of the laboratory mouse, Oxford University Press, Oxford, New York, Tokyo p 1-1807
Malkinson AM, Nesbitt MN, Skamene E (1985), Susceptibility to urethane-induced pulmonary adenomas between A/J and C57BL/6J mice: use of AXB and BXA recombinant inbred lines indicating a three-locus genetic model, Journal of the National Cancer Institute 75: 971-974
Nadeau JH, Singer JB, Matin A, Lander ES (2000), Analysing complex genetic traits with chromosome substitution strains, Nature Genetics 24: 221-225
Peters JA (1959), Classic papers in genetics, Prentice-Hall, Englewood Cliffs
Provine WB (1971), The origins of theoretical populations genetics, Chicago University Press, Chicago
Silver LM (1995), Mouse Genetics, Oxford University Press, New York, Oxford p 1-362
Snell GD (1941), Biology of the laboratory mouse, Dover, New York
Snell GD (1948), Methods for the study of histocompatibility genes, Journal of Genetics 49: 86-108
Staats J (1966), The laboratory mouse, in Biology of the Laboratory Mouse, ed. Green EL, McGraw-Hill, New York p 1-9
Strong LC (1942), The origin of some inbred mice, Cancer Research 2: 531-539
Taketo M, Schroeder AC, Mobraaten LE, Gunning KB, Hanten G, Fox RR, Roderick TH, Stewart CL, Lilly F, Hansen CT, Overbeek PA (1991), FVB/N: An inbred mouse strain preferable for transgenic analyses, Proceedings of the National Academy of Sciences 88: 2065-2069
Thomas KR, Capecchi MR (1987), Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells, Cell 51: 503-512
Travis J (1992), Scoring a technical knockout in mice, Science 256: 1392-1394
Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigo R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, LeVine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O’Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES (2002), Initial sequencing and comparative analysis of the mouse genome, Nature 420: 520-562
Whittingham DG, Leibo SP, Mazur P (1972), Survival of mouse embryos frozen to – 196C and – 269C, Science 178: 411-414