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Inbred Strains of Mice: AKR

AKR

Albino: a,B,c. Origin: a dealer named Detwiler in Norristown PA. Carried by Furth as a high-leukaemia strain from 1928 to 1936, then random bred at the Rockefeller Inst. for several generations. b x s by Mrs. Rhoades to F9 then C.Lynch to F21. This strain is best known for it's high incidence of lymphatic leukaemia, and for the Thy1a T-cell antigen, which is only present in this and a few other strains. Early history is obscure, but Acton et al (1973) found substantial substrain differences, which can best be accounted for by genetic contamination. This could have occurred at the time the strain was maintained by random mating. The strain has an international distribution, ranks about eighth in frequency of use and is widely used in cancer research for its high leukaemia incidence (Lilly and Pincus, 1973) and in immunology as a source of the Thy1.1 (theta AKR) antigen, although this varies between substrains. Mice of this strain are viraemic from birth and express in all tissues the ecotropic retrovirus AKV, copies of which are intrgrated into the genome and which is associated with the development of the leukaemia. In some substrains additional copies of the viral genomes may be integrated (Herr and Gilbert 1982). \par

Major substrains include: \par

AKR/J

Inbr ?. To Jackson Laboratory 1940. Maintained by J. \par

AKR/LwN

Inbr ?. To Law 1940, to N 1956 at F53. Maint. by N. \par

AKR/FuA

Genetically contaminated and renamed ACR/A. Maint. by A. \par

AKR/Cum

Inbr ?. Origin ?. Differs from other substrains in being Mod1a . \par

AKR/FuRdA

Oak Ridge, to ?, to Rudale, to Netherlands Cancer Institute 1953. Carries Thy1.1 and appears similar to AKR/J. \par

AKR/TlAld

Carries an autosomal translocation and has a low fertility (Leonard and DeKnudt, 1967)


Behaviour

High intrastrain aggression (2/14) (Southwick and Clark, 1966). High food drive (2/15), low emotionality (13/15) (Thompson, 1953). Long time of immobility in a forced swimming test (2/9) (Nikulina et al 1991) Susceptible to audiogenic seizures (3/11) (Fuller and Sjursen, 1967). High open-field activity (2/13) (Bruell, 1964). Low shock avoidance learning in females (5/6) (Royce et al., 1971., 1971). Low preference for sweet tasting substances (saccharin, sucrose, dulcin and acesulfame, averaged) (24/26) (Lush 1988).


Life-span and spontaneous disease

Life-span short (1/22 = 326 days in males, 276 days in females) in conventional conditions (Storer, 1966). Life-span short (1/17 = 350 days in males, 312 days in females) in fostered SPF conditions (Festing and Blackmore, 1971). \par

Lymphatic leukaemia 57% in males, 65% in females and 4% in virgin females. Mammary adenocarcinomas and primary lung tumours less than 1% (Hoag, 1963). Lymphatic leukaemia 66-87% (Festing and Blackmore, 1971). High gross tumour incidence (1/22) (Storer, 1966). Leukaemia 80-90% in females and 70-80% in males by 18 months (Nemirovsky and Trainin, 1973). Leukaemia 88% (Myers et al., 1970., 1970). Incidence of leukaemia not altered by treatment with recombinant human growth hormone (Bechensteen et al, 1993). Low incidence of leukemia (about 7% T-cell and 28% B-cell) in the AKR-Fv1b congenic strain with limited replication and spread of the N-tropic murine leukemia virus (Rosner et al, 1993, Haran-Ghera et al, 1993).


Normal physiology and biochemistry

Low metabolic rate (18/18) (Storer, 1967). High concentration of prostaglandin F in epididymis (2/6) (Badr, 1975). Low plasma cholinesterase activity (22/22) (Angel et al., 1967., 1967). Low plasma cholesterol levels (1/11) (Jiao et al 1990). High N'-methylnicotinamide oxidase activity in both sexes (2/7) (Huff and Chaykin, 1967). Low serum haptoglobin levels (11/11) (Peacock et al., 1967., 1967). High hepatic delta-aminolaevulinate dehydratase activity (1/8) (Doyle and Schimke, 1969). Low serum calcium at 7 months (6/6) (Barrett et al., 1975., 1975). High porphyrin content in Harderian gland (1/16) (Margolis, 1971). Venous blood has a high pH (1/10) (Bernstein, 1966). Blood catalase has a high specific activity (2/7) (Magdon, 1962). Resistant to the development of atherosclerosis on a semi-synthetic high fat diet (cf 5/9) (Nishina et al, 1993). Sensitive to the development of obesity associated with adipocyte sensitivity to insulin (contrast SWR/J) (Eberhart et al, 1994, West et al, 1995). Hyporesponsive to diets containing high levels of fat and cholesterol (8/9) (Kirk et al, 1995). Eat 30% more calories than SWR (resistant to high-fat dietary obesity) with a higher fat and lower carbohydrate intake (Smith et al, 1997).


Anatomy

Low testes weight (8/8) (Shire and Bartke, 1972). Large brain weight in females (13/18) (Storer, 1967). High percent carcass lipid on a high-fat diet (9/9) (West et al 1992). Large brain weight (3/25) (Roderick et al., 1973., 1973). Low total leukocyte count (14/18), high mean corpuscular volume (2/18) (Russell et al., 1951., 1951). Large relative thymus weight at 14 days (3/8), 49 days (1/8) and 90 days (1/8) (Albert et al., 1966., 1966). Large relative thymus weight (1/6) (Belyaev et al., 1970., 1970). Low relative spleen weight (9/9 to 7/9, depending on age) (Albert et al., 1966., 1966). A significant number of acinar cells of pancreas contain up to twelve nuclei (contrast seven other strains, but cf. C58) (Pollard, 1973). Carries adrenocortical lipid depletion gene which is characterised by loss of lipid vacuoles and occurrence of many closely packed mitochondria in cytoplasm of cortical cells (Arnesen, 1963). Low bone density of femur (8/11) (Beamer et al, 1996).


Drugs

High susceptibility to transplacental tumour induction by 1-ethyl-1-nitrosourea (IfS) (Diwan et al., 1973., 1973). Resistant to skin ulceration by DMBA (cf. 9/22) (Thomas et al., 1973., 1973). Resistant to toxic effects of DMBA (1/6) (Schmid et al., 1966., 1966). Resistant to teratogenic effects of 1-ethyl-1-nitrosourea (5/5) (Diwan et al., 1974., 1974). Resistant to induction of tumours by 3-methylcholanthrene (10/12) (Whitmire et al., 1971., 1971). Highly susceptible to the induction of tumours by N-Methyl-N-Nitrosourea (MNU) due to a gene on chromosome 7 (Angel et al, 1993). Sensitive to lethal effects of ozone (4/21) (Goldstein et al., 1973., 1973), but resistant (cf 3/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995). Sensitive to X-irradiation (19/27) (Roderick, 1963). Resistant to pulmonary hyaline membrane formation in 90% oxygen (2/10) (Lieberman and Kellog, 1967). High incidence of virus-like particles in chemically induced sarcomas (2/6) but low susceptibility to tumour induction by 3,4-benzpyrene (6/6) (Liebelt et al., 1970., 1970). Short sleeping time under hexobarbital anaesthetic (4/15) (Lovell, 1976), short sleeping time under pentobarbitone anaesthetic (4/23), Lovell (1986). Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7) (Evans et al., 1977., 1977). Sensitive to seizures induced by nicotine (17/19) (Marks et al 1989). Carries gene (Tpmt) for low levels of thiopurine methyltransferase activity, catalyzing the S-methylation of 6-mercaptopurine and other heterocyclic and aromaticthiol compounds (like C57BL/6, unlike DBA/2) (Otterness and Weinshilboum 1987a,b). Airways hyperreactive to acetylcholine (c.f. 3/7) (Zhang et al, 1995). A diet containing 15% dairy fat, 1% cholesterol and 0.5% cholic acid did not cause a high incidence of cholesterol gallstones (like SM, DBA/2 contrast C57L, SWR, A) (Faulkner et al, 1995)


Immunology

Sensitive to amyloid induction (3/10) but low level of spontaneous amyloid formation (Ram et al., 1969., 1969). High susceptibility to amyloid using Escherichia coli endotoxin (1/6) (Willerson et al., 1969., 1969). High lymphocyte phytohaemagglutinin response (11/43) (Heiniger et al., 1975., 1975). Good immune response to small doses of bovine gamma-globulin (cf. 4/8) (Levine and Vaz, 1970). Poor primary immune response to bacteriophage fd (6/7) (Klsch et al., 1971l., 1971). Poor splenic PFC immune response to pneumococcal polysaccharide (8/9) (Amsbaugh et al. 1972 . 1972). Good immune response to ovomucoid, but poor response to ovalbumin (cf. 5/12) (Vaz et al., 1971., 1971). Good immune response to DNP-keyhole limpet haemocyanin (2/11) (Borel and Kilham, 1974). Discriminator between `H' and `L' sheep RBC (cf. 12/18) (McCarthy and Dutton, 1975). High susceptibility to IgE-mediated passive cutaneous anaphylaxis (1/12) (De Souza et al., 1974., 1974). Susceptible to the anaphylactic death following an intravenous injection of bovine serum albumin into primed mice (Lei et al, 1996).

Erythrocytes have a high agglutinability (cf. 14/25) (Rubinstein et al., 1974., 1974). High incidence of expression of RNA tumour virus group specific antigen (1/5) (Diwan et al., 1973., 1973). Low immune response to ferritin (14/16) (Young et al., 1976., 1976). Low immune response to dextran (cf. 6/10) (Blomberg et al., 1972., 1972). Low immune response to ganglio-series gangliosides (c.f. 4/10) Kawashima et al (1992). Resistant to immunosuppression of contact hypersensitivity by ultraviolet B light (cf 4/18) (Noonan and Hoffman, 1994). High expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin A stimulated T lymphoblasts (cf 3/6) (Muthing, 1997).


Infection

Resistant to infection by the obligate intracelluar parasite Besnotia jettisoni (1/8) (Lunde and Gelderman, 1971). Susceptible to a natural intestinal helminth infection (10/10) (Eaton, 1972). Susceptible to Herpes simplex infection (11/11) (Lopez, 1975). Low mortality in a natural epizootic of ectromelia (8/8) (Briody, 1966). Resistant to induction of diabetes mellitus by encephalomyocarditis virus (cf. 7/14) (Boucher et al., 1975., 1975). Resistant (1/7) to the induction of dental caries due to infection with Streptococcus mutans (Kurihara et al 1991). Susceptible to infection with murine herpes virus (1/4) (Kapoor et al 1992). Mouse mammary tumor proviral loci have been identified by Lee and Eicher (1990). Develop severe lesions (1/8) following infection with Candida albicans (Ashman et al, 1993). Resistant (4/10) to infection with Ehrlichia risticii (Williams and Timoney, 1994). Resistant, with low amylase response to the fungus Paracoccidioides brasiliensis (cf 6/12) (Xidieh et al, 1994). Infection with larval Echinococcus multilocularis by transportal injection of hyatid homogenate results in well developed protoscoleces (cf 4/9) (Nakaya et al, 1997). Develop paralysis (age-dependent polyomyelitis) following infection with the lactate dehydrogenase-elevating virus in common with other mouse strains (e.g. C58) which possess N-tropic ecotropic murine leukemia proviruses and are homozygous Fv-1n (Anderson et al, 1995). \par \par


Reproduction

Poor reproductive performance (22/25), output 0.74 young/female/week, litter size low (22/25) at 4.1 weaned (Festing, 1976a). Intermediate breeding performance (14/24) (Hansen et al., 1973., 1973). Low post-implantation loss of embryos (1/8), but high pre-implantation losses (8/8) (Leonard et al., 1971., 1971).


Miscellaneous

Recommended host for transplantable lymphatic leukaemia BW5147 (Kaliss, 1972). High spontaneous mutation rate (4/21) (Schlager and Dickie, 1967).

AKXD-

Set of 25 recombinant inbred strains. Origin: B.A. Taylor from a cross between AKR/J and DBA/2J.

High incidence of lymphoma in most strains (Gilbert et al, 1993).

AKXL-

Set of 18 recombinant inbred strains. Inbr 15-40+. Origin: B.A.Taylor from a cross between AKR/J and C57L/J. Strain AKXL-7 has a recombinant alpha-globin gene (Lewis et al, 1993).

Maint. by Ty.


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Anderson G. W., Palmer G. A., Rowland R. R. R., Even C., and Plagemann P. G. W. (1995) Infection of central nervous system cells by ecotropic murine leukemia virus in C58 and AKR mice and in in utero-infected CE/J mice predisposes mice to paralytic infection by lactate dehydrogenase- elevating virus. Journal of Virology 69, 308-319. \par

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

Angel J. M., Morizot D. C., and Richie E. R. (1993) Localization of a novel chromosome 7 locus that suppresses development of N-methyl-N-nitrosourea-induced murine thymic lymphomas. Molecular Carcinogenesis 7, 151-156. \par

Arnesen K. (1963) The cytology of the adrenal cortex in mice with spontaneous adrenocortical lipid depletion. Acta Pathol. Microbiol. Scand. 58, 212-218. \par

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Badr F. M. (1975) Prostaglandin levels in tissues of the male reproductive system in six strains of mice. Endocrinol. 96, 540-543. \par

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Bechensteen A. G., Halvorsen S., Abdelnoor M., and Skottner A. (1993) Growth hormone treatment and development of malignancy: Recombinant human growth hormone does not induce leukemia in AKR/O-mice. Pediatric Hematology and Oncology 10, 41-47. \par

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Diwan B. A., Meier H., and Huebner R. J. (1974) Transplacental effect of 1- -ethyl-1-nitrosourea in inbred strains of mice. IV. Rapid tumoe induction in strain crosses. J. Natl. Cancer Inst. 52, 893-895. \par

Doyle D. and Schimke R. T. (1969) The genetic and developmental regulation of hepatic -aminolaevulinate dehydratase in mice. J. Biol. Chem. 244, 5449-5459. \par

Eaton G. J. (1972) Intestinal helminths in the mouse. Lab. Animal Sci. 22, 850-853. \par

Eberhart G. P., West D. B., Boozer C. N., and Atkinson R. L. (1994) Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. American Journal of Physiology - Regulatory Integrative and Comparative Physiology 266, R1423-R1428. \par

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Faulkner C. B., Davidson M. K., Davis J. K., Schoeb T. R., Simecka J. W., and Lindsey J. R. (1995) Acute Mycoplasma pulmonis infection associated with coagulopathy in C3H/HeN mice. Lab. Animal Sci. 45, 368-372. \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

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Gilbert D. J., Neumann P. E., Taylor B. A., Jenkins N. A., and Copeland N. G. (1993) Susceptibility of AKXD recombinant inbred mouse strains to lymphomas. Journal of Virology 67, 2083-2090. \par

Goldstein B. D., Lai L. Y., Ross S. R., and Cuzzi-Spada R. (1973) Susceptibility of inbred mouse strains to ozone. Arch. Environ. Health 27, 412-413. \par

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Haran-Ghera N., Peled A., Brightman B. K., and Fan H. (1993) Lymphomagenesis in AKR.Fv-1b congenic mice. Cancer Res. 53, 3433-3438. \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

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

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