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Inbred Strains of Mice: 129

129

Inbr and colour depends on substrain (see below). Origin: Dunn 1928 from crosses of coat colour stocks from English fanciers and a chinchilla stock from Castle. This strain has a common origin with strain 101. Most substrains carry the white-bellied agouti gene AW though only a subset have the agouti pattern as many carry albino or chinchilla and/or the pink-eyed dilution gene, p, which is derived from Asian mice of the Mus musculus type (see also strains SJL, P/J and FS/Ei) (Brilliant et al, 1994).

It is known for the high incidence of spontaneous testicular teratomas, though the incidence differs between substrains, but more recently it has been the most widely used strain in the production of targeted mutations due to the availability of several lines of embryonic stem cells. Two recent studies show that there is major genetic variation within the 129 "family", at least some of which must be attributed to genetic contamination (Threadgill et al, 1997,Simpson et al, 1997). Strain 129/SvJ was genetically contaminated in about 1978 by an unknown strain, and differs from other 129 substrains at about 25% of SSLP genetic markers. Threadgill et al suggest that it is equivalent to a recombinant congenic strain and suggest that it is designated 129cX/Sv. Simpson et al recognised three major groups of substrains: parental substrains, steel substrains and "ter" substrains. Threadgill et al identified substrains 129/Ola, 129/J, 129/Sv, 129/ReJ and 129/RrRk, and the associated embryonic stem cells.

Studies of 129 genealogy and genetics have resulted in major nomenclature changes for 129 substrains. See Mouse Strain 129 Substrain Nomenclature.

"Parental" substrains

129/J

129/ReJ

129/ReJ-Lama2dy

129/OlaHsd

129/Sv

129/SvJ \par \par

129/Re

Inbr (J) 89. Pale yellow: Aw,cch,p. Non-dystrophic substrain of 129/Re-dy. Maint. by Ola. \par

129/RrJ .

Inbr (J) 97. Pale yellow, or albino. Aw, cch (or c),p. Origin: Jackson Laboratory 1948. Maint. by J. \par

129/Sv-ter/+

Inbr (Sv) N8 F49. Agouti with light belly: Aw, cch, p+. Also carries a gene ter causing a high incidence of testicular teratomas. Origin: A substrain to determine the effect of the W gene on incidence of testicular teratomas. The W gene was backcrossed repeatedly to 129, and at generation N8 a female produced 38 male offspring of which 8 had testicular teratomas. All subsequent members derived from that mating. The W gene has been eliminated. Incidence of testicular teratomas now 30% (Stevens, 1973). Maint. by J.


Behaviour

Low avoidance conditionability (8/9) (Royce, 1972). Low shock-avoidance learning (6/6 in males, 5/6 in females) (Royce et al., 1971., 1971). Low preference for sweet tasting substances (saccharin, sucrose, dulcin and acesulfame, averaged, Sv substrain) (25/26) (Lush 1988). Prefers moderate concentrations of saline (contrast C57BL/6) (Beauchamp and Fisher, 1993, Gannon and Contreras, 1995).


Life-span and spontaneous disease

Long life-span in conventional conditions (18/22 = 679 days in males, 15/22 = 648 days in females) (Storer, 1966). Long life-span in SPF fostered conditions (16/17 = 699 days in males, 11/1 7 = 666 days in females) (Festing and Blackmore, 1971). Low overall tumour incidence (7% in males, 21% in females), including lymphoma 2% in males and 7% in females, soft tissue sarcomas 2% in males and 1% in females and benign tumours 2% in males and 3% in females (Smith et al., 1973., 1973). Lung tumours 4-46% (Festing and Blackmore, 1971). Testicular teratomas about 1% in most substrains, but 30% in the terSv substrain (Stevens, 1973). Incidence of teratomas increased in p53-deficient mice (Harvey et al, 1993). The Ter gene has been mapped to chromosome 18 (Asada et al, 1994). Congenital malformations about 4% in RrSvKt-jt substrain (Kalter, 1968). High incidence of urinary calculi (Russell and Meier, 1966).


Normal physiology and biochemistry

High plasma cholesterol at 12 and 24 weeks (2/8) (Weibust, 1973). Low plasma triglyceride levels (2/11) (Jiao et al 1990). High Na/K ratio in erythrocytes (1/9) and plasma (4/9) (Waymouth, 1973). High serum ceruloplasmin levels in males (3/26) but low levels in females (24/27) (Meier and MacPike, 1968). High plasma cholinesterase activity (3/22 in males, 8/22 in females) (Angel et al., 1967., 1967). Low mean heart rate (7/7) but high mean heart adaptation rate (2/7) (Blizard and Welty, 1971). High cell turnover in J substrain as estimated by rapid clearance of DNA-bound radioactivity (3/17) (Heiniger et al., 1972., 1972). Venous blood has a high pH (1/10) (Bernstein, 1966). High hepatic microsomal coumarin hydroxylase activity in females (2/8) (Van Iersel et al, 1994). High levels of apoA-IV messenger RNA in liver compared with C57BL/6 (Reue et al, 1993).

Has defective secretory group II phospholipase A2 gene (cf strains C57BL/6 and B10.RIII) (Kennedy et al, 1995).


Anatomy

Large brain/body weight ratio (3/20) (Roderick et al., 1973., 1973). Small spinal cord (21/25) (Roderick et al., 1973., 1973). Small forebrain volume (8/9) and neocortex (8/9) (Wimer et al., 1969., 1969). A large proportion of 129/Ola mice have major shunts between the hepatic portal system and the vena cava, allowing the passage of microspheres up to 50m in diameter.. These shunts are associated with resistance to Shistosoma japonicum cercariae (Coulson and Wilson 1989). High retinal ganglion cell number (19/24) in /J substrain (Williams et al, 1996). Absence of corpus callosum in about 70% of mice of the 129/J substrain. This may be related to retarded formation of the hippocampal commissure in this strain and in BALB/c mice (Livy and Wahlsten, 1997). High bone density of femur in J substrain (3/11) (Beamer et al, 1996).


Drugs

Resistant to skin ulceration by DMBA (cf. 9/22) (Thomas et al., 1973., 1973). Resistant to induction of subcutaneous tumours by 3-methylcholanthrene (10/14) (Kouri et al., 1973., 1973). Resistant to X-irradiation (1/27) (Roderick, 1963), (1/10) (Storer, 1966). Females have long sleeping time under hexobarbital anaesthetic (14/15) (Lovell, 1976). Resistant to toxic effects of isoniazid (3/10) (Taylor, 1976b). Insensitive (eosinophil response) to cortisone acetate (cf. 3/6) (Wragg and Speirs, 1952). Sensitive uterine response to oestrogens (1/5) (Chai and Dickie, 1966; Drasher, 1955). Susceptible (cf 5/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995).


Immunology

High lymphocyte phytohaemagglutinin response (12/43) (Heiniger et al., 1975., 1975). Responder to synthetic polypeptide (Glu57, Lys38, Ala5) (cf. 3/7) (Pinchuck and Maurer, 1965). Erythrocytes have a high agglutin ability (cf. 14/25) (Rubinstein et al., 1974., 1974). High responder to Dextran (cf. 4/10) (Blomberg et al., 1972., 1972). Experimental systemic lupus erythematosus including severe ocular changes and blepharitis can be induced by injection of human monoclonal anti-DNA antibodies (Chan et al, 1995).


Infection

Carries no detectable endogenous ecotropic MuLV DNA sequences (Jenkins et al 1982).


Reproduction

Poor breeding performance (19/22), colony output 0.8 young/female/wk, litter size at weaning 4.5 (19/22) (Festing, 1976a).


Miscellaneous

Recommended host for transplantable tumour haemangioendothelioma BW6473 (Kaliss, 1972).


Angel C. R., Mahin D. T., Farris R. D., and Woodward K. T. (1967) Heritability of plasma cholinesterase activity in inbred mouse strains. Science 156, 529-530. \par

Asada Y., Varnum D. S., Frankel W. N., and Nadeau J. H. (1994) A mutation in the Ter gene causing increased susceptibility to testicular teratomas maps to mouse chromosome 18. Nature Genet. 6, 363-368. \par

Beamer W. G., Donahue L. R., Rosen C. J., and Baylink D. J. (1996) Genetic-variability in adult bone-density among inbred strains of mice. Bone 18, 397-403. \par

Beauchamp G. K. and Fisher A. S. (1993) Strain differences in consumption of saline solutions by mice. Physiol. Behav. 54, 179-184. \par

Bernstein S. E. (1966) Physiological characteristics, in Biology of the Laboratory Mouse, 2nd. ed. (Green E. L., ed), pp. 337-350. McGraw-Hill, New York. \par

Blizard D. A. and Welty R. (1971) Cardiac activity in the mouse: strain differences. J. Comp. Physiol. Psychol. 77, 337-344. \par

Blomberg B., Geckeler W. R., and Weigert M. (1972) Genetics of the antibody response to Dextran in mice. Science 177, 178-180. \par

Brilliant M. H., Ching A., Nakatsu Y., and Eicher E. M. (1994) The original pink-eyed dilution mutation (p) arose in asiatic mice: Implications for the H4 minor histocompatibility antigen, Myod1 regulation and the origin of inbred strains. Genetics 138, 203-211. \par

Chai C. K. and Dickie M. M. (1966) Endocrine variations, in Biology of the laboratory mouse, 2nd. ed. (Green E. L., ed), pp. 387-403. McGraw-Hill, New York. \par

Chan C. C., Gery I., Kohn L. D., Nussenblatt R. B., Mozes E., and Singer D. S. (1995) Periocular inflammation in mice with experimental systemic lupus erythematosus: A new experimental blepharitis and its modulation. J. Immunol. 154, 4830-4835. \par

Coulson P. S. and Wilson R. A. (1989) Portal shunting and resistance to Shistosoma mansoni in 129 strain mice. Parasitology 99, 383-389. \par

Festing M. F. W. and Blackmore D. K. (1971) Life span of specified-pathogen-free (MRC category 4) mice and rats. Lab. Anim. 5, 179-192. \par

Gannon K. S. and Contreras R. J. (1995) Sodium intake linked to amiloride-sensitive gustatory transduction in C57BL/6J and 129/J mice. Physiol. Behav. 57, 231-239. \par

Harvey M., McArthur M. J., Montgomery C. A., Bradley A., and Donehower L. A. (1993) Genetic backgound alters the spectrum of tumors that develop in p53-deficient mice. FASEB 7, 938-943. \par

Heiniger H. J., Chen H. W., Meier H., Taylor B. A., and Commerford L. S. (1972) Studies on the genetic control of cell proliferation. 1. Clearance of DNA-bound radioactivity in 19 inbred strains and hybrid mice. Life Sci. 11, 87-98. \par

Heiniger H. J., Taylor B. A., Hards E. J., and Meier H. (1975) Heritability of the phytohaemagglutinin responsiveness of lymphocytes and its relationship to leukemogenesis. Cancer Res. 35, 825-831. \par

Jenkins N. A., Copeland N. G., Taylor B. A., and Lee B. K. (1982) Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J. Virol. 43, 26-36. \par

Jiao S., Cole T. G., Kitchens R., Pfleger B., and Schonfeld G. (1990) Genetic heterogeneity of lipoproteins in inbred strains of mice: analysis by gel-permeation chromatography. Metabolism 39, 155-160. \par

Kalter H. (1968) Sporadic congenital malformations of newborn inbred mice. Teratology 1, 193-200. \par

Kennedy B. P., Payette P., Mudgett J., Vadas P., Pruzanski W., Kwan M., Tang C., Rancourt D. E., and Cromlish W. A. (1995) A natural disruption of the secretory group II phospholipase A2 gene in inbred mouse strains. J. Biol. Chem. 270, 22378-22385. \par

Kouri R. E., Salerno R. A., and Whitmire C. E. (1973) Relationships between arylhydrocarbon hydroxylase inducibility and sensitivity to chemically induced subcutaneous sarcomas in various strains of mice. J. Natl. Cancer Inst. 50, 363-368. \par

Livy D. J. and Wahlsten D. (1997) Retarded formation of the hippocampal commissure in embryos from mouse strains lacking a corpus callosum. Hippocampus 7, 2-14. \par

Lush I.M. (1988) The genetics of tasting in mice. VI. Saccharin, acesulfame, dulcin and sucrose. Genet. Res. 53, 95-99. \par

Meier H. and MacPike A. D. (1968) Levels and heritability of serum ceruloplasmin activity in inbred strains of mice. Proc. Soc. Exp. Biol. Med. 128, 1185-1190. \par

Pinchuck P. and Maurer P. H. (1965) Antigenicity of polypeptides (poly alpha amino acids). XVI. Genetic control of immunogenicity of synthetic polypeptides in mice. J. Exp. Med. 122, 673-679. \par

Reue K., PurcellHuynh D. A., Leete T. H., Doolittle M. H., Durstenfeld A., and Lusis A. J. (1993) Genetic variation in mouse apolipoprotein A-IV expression is determined pre- and post-transcriptionally. J. Lipid Res. 34, 893-903. \par

Roderick T. H., Wimer R. E., Wimer C. C., and Schwartzkroin P. A. (1973) Genetic and phenotypic variation in weight of brain and spinal cord between inbred strains of mice. Brain Res. 64, 345-353. \par

Roderick T. H. (1963) The response of twenty-seven inbred strains of mice to daily doses of whole-body X-irradiation. Radiation Res. 20, 631-639. \par

Royce J. R., Yeudall L. T., and Poley W. (1971) Diallel analysis of avoidance conditioning in inbred strains of mice. J. Comp. Physiol. Psychol. 76, 353-358. \par

Royce J. R. (1972) Avoidance conditioning in nine strains of inbred mice using optimal stimulus parameters. Behav. Genet. 2, 107-110. \par

Rubinstein P., Liu N., Strenn E. W., and Decary F. (1974) Electrophoretic mobility and agglutinability of red blood cells: a `new' polymorphism in mice. J. Exp. Med. 139, 313-322. \par

Russell E. S. and Meier H. (1966) Constitutional diseases, in Biology of the Laboratory Mouse, 2nd. ed. (Green E. L., ed), pp. 571-587. McGraw-Hill, New York. \par

Simpson E. M., Linder C. C., Sargent E. E., Davisson M. T., Mobraaten L. E., and Sharp J. J. (1997) Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nature Genet. 16, 19-27. \par

Smith G. S., Walford R. L., and Mickey R. M. (1973) Lifespan and incidence of cancer and other diseases in selected long-lived inbred mice and their F1 hybrids. J. Natl. Cancer Inst. 50, 1195-1213. \par

Stevens L. C. (1973) A new inbred subline of mice (129/ter, Sv) with a high incidence of spontaneous congenital testicular teratomas. J. Natl. Cancer Inst. 50, 235-242. \par

Storer J. B. (1966) Longevity and gross pathology at death in 22 inbred strains of mice. J. Gerontol. 21, 404-409. \par

Takahashi M., Kleeberger S. R., and Croxton T. L. (1995) Genetic control of susceptibility to ozone-induced changes in mouse tracheal electrophysiology. American Journal of Physiology - Lung Cellular and Molecular Physiology 269, L6-L10. \par

Thomas P. E., Hutton J. J., and Taylor B. A. (1973) Genetic relationship between aryl hydrocarbon hydroxylase inducibility and chemical carcinogen induced skin ulceration in mice. Genetics 74, 655-659. \par

Threadgill D. W., Yee D., Matin A., Nadeau J. H., and Magnuson T. (1997) Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm. Genome 8. \par

Van Iersel M., Walters D. G., Price R. J., Lovell D. P., and Lake B. G. (1994) Sex and strain differences in mouse hepatic microsomal coumarin 7- hydroxylase activity. Food and Chemical Toxicology 32, 387-390. \par

Waymouth C. (1973) Erythrocyte sodium and potassium levels in normal and anaemia mice. Comp. Biochem. Physiol. 44A, 751-766. \par

Weibust R. S. (1973) Inheritance of plasma cholesterol levels in mice. Genetics 73, 303-312. \par

Williams R. W., Strom R. C., Rice D. S., and Goldowitz D. (1996) Genetic and environmental-control of variation in retinal ganglion-cell number in mice. Journal of Neuroscience 16, 7193-7205. \par

Wimer R. E., Wimer C. C., and Roderick T. H. (1969) Genetic variability in forebrain structures between inbred strains of mice. Brain Res. 16, 257-264. \par

Wragg L. E. and Speirs R. S. (1952) Strain and sex differences in response of inbred mice to adrenal cortical hormones. Proc. Soc. Exp. Biol. Med. 80, 680-684. \par


INBRED STRAINS OF MICE
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK

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