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Inbred Strains of Mice: A

A

Inbr: More than F150. Albino. Genet: a, b, c. Origin: Dr L. C. Strong, 1921, from a cross between the Cold Spring Harbor and Bagg albino random-bred stocks (and therefore relavted to BALB/c). Internationally distributed, Strain A was the third most widely used strain in cancer and immunology research (Festing, 1969), though its popularity has probably declined recently. Although it may be classified as a general-purpose strain, it is well known for a high susceptibility to induction of congenital cleft palate by cortisone and a high spontaneous incidence of lung adenomas, as well as developing a high incidence of lung tumours in response to carcinogens. Shimkin and Stoner (1975) suggest that this response may be used as a rapid in vivo assay for carcinogenesis. The strain also suffers from a defect in macrophage function somewhat resembling the mutant lps found in C3H/HeJ (Vogel et al 1981).

The following main substrains are recognised, though they have not been defined by genetic markers:

A/St

Maintained by Strong.

A/He

Strong to Heston, 1938.

A/GrFa

Main British substrain, Strong to Gruneberg 1932, and mainly distributed by Falconer.

A/WySn

Strong to Bittner 1927, to Wooley, to Snell, 1951.

A/J

Strong to Cloudman 1928, to Jackson Laboratory 1947, now widely distributed.


Behaviour

Low intra-strain aggression (13/14) (Southwick and Clark, 1966), low food drive (15/15) and exploratory activity (15/15) (Thompson, 1953). Low spontaneous bar pressing activity (12/14), low open-field activity (13/14 and 14/14 in J and He substrains), low social grooming during aggressive encounters (12/14 in He substrain) and high tail rattling score (3/14 and 5/14 in J and He substrains) during aggressive encounters (Southwick and Clark, 1968). Low spontaneous locomotor activity (2/9) (Nikulina et al 1991). High shock avoidance learning (3/9) (Bovet et al., 1966., 1966), high avoidance conditioning (2/9) (Royce, 1972), and (2/6 males, 1/6 females) (Royce et al., 1971., 1971), but poor shock avoidance learning (8/8) (Wahlsten, 1973), poor T-maze learning (6/6) (Stasik, 1970). Long latency to attack crickets (7/7) (Butler, 1973). Long latency to emerge from home cage (7/7), low exploration in Y-maze (6/7), low rearing (6/7), long latency to climb barrier (7/7), low hole-in-the-wall entry (7/7), low stair climbing (6/7) (McClearn et al., 1970., 1970). Poor shock avoidance conditioning (6/7 and 7/7 in He and J substrains) and rapid extinction (1/7 and 2/7 in J and He substrains) (Schlesinger and Wimer, 1967). Poor performance in a food-seeking task (6/6) (Henderson, 1970). High social dominance of males in competition for females (1/6) (De Fries and McClearn, 1970). High open-field defaecation (1/5) in both sexes (Bruell, 1969). Low open- field activity (12/13) (Bruell, 1964). Low proportion of paradoxical sleep (6/7) (Pagel et al., 1973., 1973), low incidence of tail rattling (5/5) (St. John, 1973). High shuttle box avoidance (1/5) (Messeri et al., 1972., 1972). Low wheel activity (5/5) (Messeri et al., 1972., 1972), low alcohol preference (15/18) (Rodgers, 1966).

Life-span and spontaneous disease

Primary lung tumours 6% in male, 32% in female and 26% in virgin females in J substrain; 44% in males, 23% in females and 30% in virgin females in He substrains (Hoag, 1963). Zero incidence of lymphatic leukaemia in He substrain, 1% in J substrain. Mammary adenocarcinomata zero in males, 1% in virgin females, 28% in breeding females of J substrain and 54% in breeding females of He substrain (Hoag, 1963). Pulmonary tumours 90% in mice at 18 months (Heston, 1963). Leukaemia 3% in HeJ substrain (Myers et al., 1970., 1970). A high proportion of the mammary tumours are of the acinar type (3/7) (Tengbergen, 1970). Lung adenomas 53-64% in BrA and A substrains, but mammary tumours zero (Muhlbock and Tengbergen, 1971). Lung tumours 4-31% and lymphatic leukaemia 10-43% (Festing and Blackmore, 1971). Spontaneous lung tumours occur at rate of 0.21 tumours/mouse at 24 weeks (Poirier et al., 1975., 1975). Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed in the J and HeJ substrains (Sundberg et al 1991)

Life-span in conventional conditions intermediate in both sexes (9/22 = 490 days in males, 13/22 = 590 days in females (Storer, 1966). Life-span in SPF fostered conditions intermediate (8/17 = 512 days) in males and short (3/17 = 558 days) in females (Festing and Blackmore, 1971). Life-span 662 days in males and 688 days in females (Goodrick, 1975). Median life-span 400 days in HeJ substrain (Curtis, 1971).

Spontaneous congenital cleft palate 4% and high susceptibility to teratogenic effects of cortisone, which may be associated with the H2a allele, (Bonner and Slavkin, 1975). Congenital malformations in new-born mice 10% (1/9), including cleft lip and palate and polydactyly (Kalter, 1968). WySn substrain has 20% cranofacial defects due to the action of two genetic loci with unequal duplicate epistasis (Juriloff, 1995). Cleft palate is a function of foetal genotype rather than maternal factors (Yoshida et al, 1996). An exclusion map for the major gene causing nonsyndromic cleft lip with or without cleft palate has swept 40% of the mouse genome, with candidate regions on chromosomes 12, 18 and 19 with a few candidate loci (Juriloff, 1993).

Low incidence of virus-like particles in chemically induced sarcomas (6/6) (Liebelt et al., 1970., 1970). Can be made obese by a suitable diet (Fenton and Dowling, 1953). Does not develop non-insulin-dependent diabetes mellitus and hypertension when fed a high fat-high simple carbohydrate diet, whereas C57BL/6 mice do (Mills et al 1993). Blood glucose levels and insulin insensitivity in crosses between diet-induced type II diabetes sensitive C57BL/6 and resistant A/J are genetically independent (Surwit et al 1991)

High incidence of amyloidosis (Russell and Meier, 1966). No amyloidosis found by Powers et al. (1976) in He and HeJ substrains, in contrast to previous reports. About 4% incidence of congenital open eyelids (Dagg, 1966). High incidence of cannibalism of young restricted to anatomically defined mutilation and amputation, particularly of neck, lower jaw and digits in Ha substrain (Hauschka, 1952).

Relatively resistant to secondary amyloidosis which does not appear to be associated with variation in the serum amyloid A gene cluster (Butler and Whitehead, 1994).

Normal physiology and biochemistry

Low metabolic rate (16/18) (Storer, 1967). High plasma testosterone level and binding capacity (1/5) (Hampl et al., 1971., 1971). Low Na/K ratio in erythrocytes (7/9) and plasma (8/9) (Waymouth, 1973). Low serum ceruloplasmin in males (23/26) but intermediate in females (Meier and MacPike, 1968).

Low systolic blood pressure (17/19) (Schlager and Weibust, 1967). Low peripheral nerve conduction velocity (5/6) (Hegmann, 1972). High concentration of prostaglandin F in epididymis (1/6) (Badr, 1975). High glucose-6-phosphate dehydrogenase and nicotinamide-adenine dinucleotide phosphate levels in erythrocytes (1/8) (Erickson, 1974). High sensitivity to thyrotrophin (2/21) (Levy et al., 1965., 1965). Mammary gland insensitive to oestradiol and progesterone (1/7) (Singh et al., 1970., 1970). High glucose-6-phosphate dehydrogenase activity (1/16) (Hutton, 1971). High brain acetylcholinesterase activity (1/5) (Pryor et al., 1966., 1966).

High rectal (1/9) but low tail temperature (9/9) (Shepard and Habas, 1967). Low serum calcium level at 4 months of age (6/6) (Barrett et al., 1975., 1975). Responds by higher growth rate on high fat diets (1/4) (Fenton and Carr, 1951). Low cell turnover as estimated by slow clearance of DNA-bound radioactivity (16/17 and 15/17 in J and He substrains, respectively) (Heiniger et al., 1972., 1972). High erythrocyte catalase level (4/18) (Hoffman and Rechcigl, 1971). Low kidney (11/12) and liver (10/12) arylsulphatase activity (Daniel, 1976). High hepatic delta-aminolaevulinic acid synthetase activity after DISC treatment (4/15 in He substrain, 5/15 in J substrain) (Gross and Hutton, 1971). High basal serum prolactin level in females of St substrain (2/6) (Sinha et al., 1975., 1975). Urine has high osmolality (2/7) (Silverstein, 1961). Blood catalase has high specific activity (1/7) (Magdon, 1962). Resistant to the development of atherosclerosis on a semi-synthetic high fat diet (cf 5/9) (Nishina et al, 1993).


Anatomy

High percent carcass lipid on a high-fat diet (7/9) (West et al 1992). Small spinal cord (25/25), small brain/body weight ratio (16/20) (Roderick et al., 1973., 1973). Small relative kidney size (20/21) (Schlager, 1968). Low total leukocyte count (16/18), low erythrocyte count (18/18 J substrain, 17/18 He substrain), low haematocrit (17/18), low haemoglobin per 100 cm3 blood (16/18 He substrain, 14/18 J substrain) (Russell et al., 1951., 1951). Small thymus/body weight ratio (6/6) (Belyaev et al., 1970., 1970). Low proportion acidophilic (5/5) and high proportion chromophobe cells in adenohypophysis (Keramidas and Symeonidis, 1973). High frequency of mast cells in spleen also found in A.CA and A.SW (1/14) (Vicklicky, 1967). Low yield of peritoneal exudate cells (5/5) with low percentage of macrophages (5/5) and granulocytes (5/5) but high percentage of lymphocytes (1/5) (Schwartz et al., 1975., 1975). Adrenal gland has a high incidence of vacuolisation of the X-zone (1/6) (Delost and Chirvan-Nia, 1958). Small pituitary (6/6) (Sinha et al., 1975., 1975). Number of nipples commonly less than five pairs. Small number of Peyer's patches (6/7) (Hummel et al., 1966., 1966). Lower bone mass than C57BL/6 (Kaye and Kusy, 1995). Low retinal ganglion cell number (4/24) (Williams et al, 1996).


Drugs

Susceptible to urethane-induced lung tumours (1/6) (Falconer and Bloom, 1962). Sensitive to induction of pulmonary tumours (1/6) but resistant to leukaemia and liver tumour induction by DMBA given neonatally (6/6 and 5/6, respectively) (Flaks, 1968). Susceptible to the induction of lung tumours by cyclopenta(cd)pyrene (Nesnow et al, 1994). Most benzo(a)pyrine-induced lung tumours had K-ras oncogenes inherited from the A/J parent with mRNA transcribed from the allele inherited from strain A/J being 5-20 times more abundant than that from C3H in crosses involving strain C3H (Chen et al, 1994) The A/J mouse lung can be used as a model to study the effectiveness of new chemical intervention therapies for controlling malignant tumor growth (Belinsky et al, 1993), and in the study of chemopreventive agents such as dietary and green tea polyphenols (Castonguay and Packer, 1993, Katiyar et al, 1993), isothiocyanates (AdamRodwell et al, 1993, Hecht, 1995), vitamin E (Yano et al, 1994) and other substances (Yun et al, 1995). No glycerol-associated effect on active oxygen formation and thiobarbituric acid reactive substances was observed in the lungs of A/J mice treated with 4-nitroquinoline 1-oxide, in contrast with outbred ddY strain mice (Yano et al, 1993, 1994).

Nicotine decreases shock avoidance learning in J substrain (7/9), but increases it in He substrain (2/9) (Bovet et al., 1966., 1966). Low ED50 to behavioural effects of nicotine (2/19). Resistant to seizures induced by nicotine (2/19) (Marks et al 1989) Susceptible to skin ulceration by DMBA (cf. 13/22) (Thomas et al., 1973., 1973). Not sensitive to histamine (8/9) (Brown, 1965). Susceptible to the teratogenic effect (cleft palate) of cortisone acetate (1/4) (Dostál and Jel\'92; Kalter, 1965lter, 1965, Kalter 1981). There appears to be a threshold dose of cortisone needed to induce cleft palate (Fawcett et al, 1996).

Sensitive to teratogenic effect (malformed ribs and vertebrae) of hypoxia on ninth day of gestation (1/5) (Dagg, 1966). Sensitive to X-irradiation (22/27 in He substrain, 20/27 in J substrain) (Roderick, 1963), 9/10 in males, 8/10 in females of J substrain (Storer, 1966). Highly susceptible to endotoxin lipopolysaccharide (1/5) (Heppner and Weiss, 1965). Resistant to hyperbaric oxygen (15/18 in J substrain, 12/18 in He substrain) (Hill et al., 1968., 1968). Susceptible to pulmonary hyaline-membrane formation in 90% oxygen (3/10) (Lieberman and Kellog, 1967). Low LD50 to X-irradiation (7/9) (Yuhas and Storer, 1969). Interstitial tumours of testis readily induced with oestrogens (Heston, 1963). Sensitive to chloroform toxicity (cf. 4/9) (Deringer et al., 1953., 1953). Thalidomide increases congenital malformations such as cleft lip and palate (Szabo and Steelman, 1967)..High bronchial reactivity (1/6) to methacholine and serotonin (Konno et al 1993). Susceptible (1/8) to daunomycin-induced nephorsis (Kimura et al 1993). Resistant to hepatotoxic effects of cadmium (Shaikh et al, 1993). Airways hyperreactive to acetylcholine (c.f. 3/7) (Zhang et al, 1995). Susceptible (cf 5/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995). Clonidene failed to produce an aggressive behavioural response (cf 3/9) (Nikulina and Klimek, 1993). A diet containing 15% dairy fat, 1% cholesterol and 0.5% cholic acid caused a high incidence of cholesterol gallstones (like SWR, C57L, contrast SM, AKR, DBA/2) (Faulkner et al, 1995).


Immunology

Develops autoimmune phenomena, immunological deficits with ageing and autoimmunity following neonatal thymectomy (Yunis et al., 1972., 1972). Low lymphocyte phytohaemagglutinin response (32/43) (Heiniger et al., 1975., 1975). Serum antinuclear factor 11% (7/18) (Barnes and Tuffrey, 1967). 11% incidence of antinuclear antibody by 16 months (1/17 in J substrain) (Teague et al., 1972., 1972). Good immune response to small doses of bovine gamma-globulin (cf. 4/8) (Levine and Vaz, 1970). Poor immune response to Cholera A and B antigens (7/9A, 6/8B) (Cerny et al., 1971., 1971). Good immune response to ovomucoid but poor response to bovine serum albumin (1/6) (James and Milne, 1972). Good immune response to DNP-keyhole limpet haemocyanin (1/33 in J substrain, 3/11 in He substrain) (Borel and Kilham, 1974). Good immune response to GAT (random terpolymer of Glu60, Ala30, Tyr10) (1/10 in He substrain, 3/10 in J substrain) (Dorf et al., 1974., 1974). Poor primary haemagglutinin immune response to sheep erythrocytes at 3 x 107 and 3 x 108 dose rates (6/6 and 5/6, respectively), also poor haemolysin response at both doses (6/6) (Ghaffar and James, 1973). High IgM antibody response to sheep red blood cells compared with C57BL/10ScSn (Vetvicka et al, 1993). Non-responder to synthetic polypeptide Glu57, Lys38, m-Ala5 (cf. 4/7) (Pinchuck and Maurer, 1965). High antibody affinity to HSA (1/9) (Petty et al, 1972 , 1972). Erythrocytes have a high agglutinability (cf. 14/25) (Rubinstein et al., 1974., 1974). Low immune response to ferritin in A-Thy1.1 (16/16) (Young et al., 1976., 1976). Low responder to dextran (cf. 6/10) (Blomberg et al., 1972., 1972). Non-discrimination between `H' and `L' sheep erythrocytes (cf. 6/18) (McCarthy and Dutton, 1975). Susceptible (1/12) to experimental autoimmune orchitis induced by two or three sc injections with viable syngeneic testicular germ cells without any adjuvants (Tokunaga et al 1993). Resistant to ineduction of experimental allergic encephalomyelitis (10/10) (Lindsey, 1996). High immune response to ganglio-series gangliosides (c.f. 2/10) Kawashima et al (1992).

Interleukin-3 alone does not support hematopoetic colony formation of bone marrow cells from these mice. Interleukin-3R alpha is not detectible on the cell surface by antibody staining, though it is present inside the cells (Ichihara et al, 1995, Leslie et al, 1996)). High immunological response to Salmonella typhi porins (2/4) (Gonzales et al, 1995)


Infection

Resistant to infection by Salmonella typhimurium strain C5 (6/7) (Plant and Glynn, 1974), (5/5) Robson and Vas (1972). This may be associated with activation of complement (Nakano et al, 1995). 100-fold more susceptible to Listeria monocytogenes than C57BL/6 when measured by median lethal does (Sadarangani et al 1980). This seems to be associated with reduced levels of gamma interferon and granulocyte-macrophage colony stimulating factor compared with resistant C57BL/6 mice (Iizawa et al, 1993). Susceptible to Plasmodium berghei (3/8) (Most et al., 1966., 1966). Highly susceptible to mammary tumour virus, which is carried in an acute form in unfostered substrains (Murray and Little, 1967). High susceptibility to BALB/Tennant leukaemia virus (2/12) (Tennant, 1965). Susceptible to Herpes simplex virus (9/11) (Lopez, 1975). Resistant to oncogenic effects of polyoma virus given at birth (Law, 1966a). Susceptible to Mycobacterium marinum (1/9) but poor plateau harvest of M. leprae 8 months after infection (7/9) (Shepard and Habas, 1967). Susceptible to infection by Mycobacterium marinum (2/6) (Yamamoto et al 1991). Resistant to mouse hepatitis virus type 3 infection (1/12 in J substrain and 2/12 in Orl substrain) though Ps substrain susceptible (Le Prevost et al., 1975., 1975). High mortality in a natural epizootic of ectromelia (1/8) (Briody, 1966). Resistant to mouse hepatitis virus (Bang and Warwick, 1960). Susceptible (1/10) 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).

Encephalomyocarditis virus causes diabetes mellitus (cp. 7/14) (Boucher et al., 1975., 1975). Highly susceptible to infection by measles virus (cf. 3/6) (Rager-Zisman et al., 1976., 1976). Legionella pneumophila replicates within and kills thioglycolate-elicited macrophages, in contrast with strain BALB/c. This is associated with differences in availability of intracellular iron (Gebran et al, 1994). Develop acute pneumonia that resembles human Legionnaire's disease 24 to 48 hours after intratracheal inoculation of Legionella pneumophila (Brieland et al, 1994). Susceptibility to most strains of Legionella depends on the Lgn1 locus (Miyamoto et al, 1996). Resistant to the lethal effects of murine hepatitis virus strain 3 (contrast BALB/c), but resistance destroyed by methylprednisolone (Fingerote et al, 1995). Highly susceptible to infection with Candida albicans (1/6) (Ashman et al,1996)


Reproduction

Intermediate breeding performance (16/26), colony output 0.9 young per female per week, litter size at weaning low at 4.4(21/25) (Festing, 1976a). Intermediate breeding performance (6/8), litter size 4.9, sterility 11.5%(Nagasawa et al., 1973., 1973). Low litter size (5/6) and large proportion of infertile matings (5/6) (Fernandes et al., 1973., 1973). Low litter size (5/6 and 4/6 in He substrain, J substrain) (Verley et al., 1967., 1967). Intermediate breeding performance (10/24) (Hansen et al., 1973., 1973). High ratio of females at birth (1/11) (Cook and Vlcek, 1961). dba/2


Miscellaneous

Recommended host for the following transplantable tumours: anaplastic carcinoma 15091 AK, hepatoma H6, round cell tumour C 1300 and spindle cell sarcoma Sal (Kaliss, 1972). Injection of murine C-1300 neuroblastoma cells derived from strain A/J into the tail vein provides a reproducible model for bone marrow metastasis (Iwakawa et al, 1994)


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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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