RIII

Inbr 80+. Albino: A,c. Origin: Dobrovolskaia-Zavadskaia, Inst. du Radium, Paris 1928, then see below. High mammary tumour incidence in unfostered substrains.

The following substrains are recognised:

RIII.

Origin as above.

RIII/An.

Dobrovolskaia-Zavadskaia to Andervont.

RIII/SeA.

From Severi (Perugia) to Muhlbock (Amsterdam) 1964. Differs from the other substrains at the Hbb and Mup loci

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Behaviour

Short latency to emerge from home cage (2/7), high rearing in Y-maze (2/7), high hole-in-the-wall entries (1/7), high exploration in Y-maze (2/7), high number of stairs climbed (2/7) and low urination score (7/7) (McClearn et al., 1970., 1970).

Life-span and spontaneous disease

Long life-span in conventional conditions (19/22 = 685 days in males, 16/22 = 655 days in females) (Storer, 1966). High incidence (88%) of mammary tumours in breeding females (Heston, 1963), but a low proportion are of the acinar type (7/7) (Tengbergen, 1970). Ovarian tumours 60% in breeding females, 50% in virgin females (Murphy, 1966). Mammary tumours 96% at 9 months (Schlom et al., 1973., 1973), 70% at 12 months (Seman and Dmochowski, 1973). Has been known to loose the mammary tumour virus spontaneously (Andervont and Dunn, 1962).

Normal physiology and biochemistry

High plasma cholinesterase activity (6/22 in females, 4/22 in males) (Angel et al., 1967., 1967). Mammary gland sensitive to oestradiol and progesterone (1/7) (Singh et al., 1970., 1970). High brain cholinesterase activity (1/5) (Pryor et al., 1966., 1966).

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Anatomy

Small kidney/body weight ratio (18/21) (Schlager, 1968). Low total leukocyte count (17/18), low erythrocyte count (15/18), high mean corpuscular volume (4/18) (Russell et al., 1951., 1951). High proportion of basophilic cells in adenohypophysis (1/5) (Keramidas and Symeonidis, 1973). Adrenal gland has a small X zone (8/8), with a low incidence of vacuolisation (6/6) (Delost and Chirvan-Nia, 1958).

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Drugs

Sensitive to X-irradiation (24/27) (Roderick, 1963). Low susceptibility to endotoxin lipopolysaccharide (5/5) (Heppner and Weiss, 1965).

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Immunology

High lymphocyte phytohaemagglutinin response (5/43) (Heiniger et al., 1975., 1975). Erythrocytes have a high agglutinability (cf. 14/25) (Rubinstein et al., 1974., 1974).

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Reproduction

Poor reproductive performance (7/8), litter size 6.1 _ 0.2 and sterility 31% (Nagasawa et al., 1973., 1973).

RIIIS

In 1967 both RIII and RIII/An maintained at The Jackson Laboratory failed to produce viable young. RIII/2J was developed from a cross between the two substrains. Name later changed to RIIIS. High serum complement activity (c.f. 8/26) (Ong et al 1989)

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Characteristics

RIIIS carries no detectable endogenous ecotropic MuLV DNA sequences (Jenkins et al 1982). High ED50 to behavioural effects of nicotine (16/19) (Marks et al 1989). Has the largest known deletion of the T cell receptor (TCR) V beta genes, having lost approximately 130 kb of V beta chromosome and with it 13 V beta genes out of the known 21 V beta genes of the TCR. The deletion is marked by the presence of V beta 10 gene upstream and V beta 3 gene downstream. (Haqqi et al 1989).

Develops a condition resembling human type I von Willebrand's disease characterised by a prolonged bleeding time, normal von Willebrand factor multimer (VWF) distribution, autosomal dominant inheritance and proportionally decreased plasma von Willebrand factor antigen and factor VIII activity. The disease is caused by a genetic defect at a locus distinct from the murine von Willebrand factor gene (Nichols et al, 1994). A single dominant modifier locus (Mvwf) on distil chromosome 11 accounted for 63% of variation in plasma VWF levels in a cross with CASA/Rk. This is distinct from the Vwf locus on chromosome 6 (Mohlke et al, 1996).

Resistant to the induction of arthritis by type II collagen (Ortman et al, 1994). Carries two mutations causing defects in cortosteroid-binding globulin (Orava et al, 1994).

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Andervont H. B. and Dunn T. B. (1962) Studies of the mammary tumor agent of strain RIII mice. J. Natl. Cancer Inst. 28, 159-185.

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.

Delost P. and Chirvan-Nia P. (1958) Differences raciales dans l'involution de la zone x multi surrenalienne chez la souris adulte vierge. C. R. Soc. Biol. 152, 453-455.

Haqqi T. M., Banerjee S., Anderson G. D., and David C. S. (1989) RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. J. Exp. Med. 169, 1903-1909.

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.

Heppner G. and Weiss D. W. (1965) High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures. J. Bacteriol. 90, 696-703.

Heston W. E. (1963) Genetics of neoplasia, in Methodology in mammalian genetics (Burdette W. J., ed), pp. 247-268. Holden-Day, San Francisco.

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.

Keramidas G. D. and Symeonidis A. (1973) Characteristic microscopic differences in the adenohypophysis of high and low mammary tumour strains of mice. Pathol. Eur. 8, 35-36.

Marks M. J., Stitzel J. A., and Collins A. C. (1989) Genetic influences on nicotine responses. Pharmacol. Biochem. Behav. 33, 667-678.

McClearn G. E., Wilson J. R., and Meredith W. (1970) The use of isogenic and heterogenic mouse stocks in behavioral research, in Contribution to behavior genetic analysis. The mouse as a prototype (Lindzey G. and Thiessen D. D., eds), pp. 3-32. Appleton-Century-Crofts, New York.

Mohlke K. L., Nichols W. C., Westrick R. J., Novak E. K., Cooney K. A., Swank R. T., and Ginsburg D. (1996) A novel modifier gene for plasma von Willebrand factor level maps to distal mouse chromosome 11. Proceedings of the National Academy of Sciences of the United States of America 93, 15352-15357.

Murphy E. D. (1966) Characteristic tumors, in Biology of the laboratory mouse, 2nd. ed. (Green E. L., ed), pp. 521-562. McGraw-Hill, New York.

Nagasawa H., Miyamoto M., and Fujimoto M. (1973) Reproductivity in inbred strains of mice and project for their efficient production. Exp. Animals (Japan) 22, 119-126.

Nichols W. C., Cooney K. A., Mohlke K. L., Ballew J. D., Yang A., Bruck M. E., Reddington M., Novak E. K., Swank R. T., and Ginsburg D. (1994) von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. Blood 83, 3225-3231.

Ong G. L. and Mattes M. J. (1989) Mouse strains with typical mammalian levels of complement activity. J. Immunol. Methods 125, 147-158.

Orava M., Zhao X. F., Leiter E., and Hammond G. L. (1994) Structure and chromosomal location of the gene encoding mouse corticosteroid-binding globulin: Strain differences in coding sequence and steroid-binding activity. Gene 144, 259-264.

Ortman R. A., Holderbaum D., Qu X. M., Banerjee S., and Haqqi T. M. (1994) BUB/BnJ (H-2(q)) is a TCR deletion mutant mouse strain (TCR Vbetaa, KJ16- ) that is susceptible to type II collagen-induced arthritis. J. Immunol. 152, 4175-4182.

Pryor G. T., Schlesinger K., and Calhoun W. H. (1966) Differences in brain enzymes among five inbred strains of mice. Life Sci. 5, 2105-2111.

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.

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.

Russell E. S., Neufeld E. F., and Higgins C. T. (1951) Comparison of normal blood picture of young adults from 18 inbred strains of mice. Proc. Soc. Exp. Biol. Med. 78, 761-766.

Schlager G. (1968) Kidney weight in mice: strain differences and genetic determination. J. Hered. 59, 171-174.

Schlom J., Michalides R., Kufe D., Hehlmann R., Spiegelman S., Bentvelzen P., and Hageman P. (1973) A comparative study of the biological and molecular basis of murine mammary carcinoma. A model for human breast cancer. J. Natl. Cancer Inst. 51, 541-551.

Seman G. and Dmochowski L. (1973) Viropexis of type B particles in reticulum cell sarcoma of RIII/Om strain mice. Cancer Res. 33, 1238-1246.

Singh D. V., DeOme K. B., and Bern H. A. (1970) Strain differences in response of the mouse mammary gland to hormones in vitro. J. Natl. Cancer Inst. 45, 657-675.

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

Tengbergen W. J. P. R. van E. (1970) Morphological classification of mammary tumours in the mouse. Path. Eur. 5, 260-272.

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