A2G

Inbr: F 101. Albino. Genet: b, c. Originated as an illegitimate mating of strain A at Glaxo Laboratories, UK, in 1942-50, followed by b x s mating. Should not be considered as a substrain of A. Distributed mainly in European laboratories, and best known for its unique resistance to myxovirus (influenza) infections.

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Behaviour

Whisker chewing 75% in cages of 2-3 mice by 60 days of age. Whisker trimming seems to be associated with social dominance (Strozik and Festing 1981). Low balsa-wood gnawing activity (3/16) in A2G-hrhr, but high activity in A2G (1/16) (Fawdington and Festing 1980). It is not prevented by offering the mice means of withdrawal from it (Van den Broek et al, 1993).

Life-span and spontaneous disease

Long life-span in males (13/17 = 640 days) but intermediate in females (8/17 = 644 days), and lung tumours 17-65% in SPF fostered conditions (Festing and Blackmore, 1971).

Normal physiology and biochemistry

High incidence of audiogenic seizures (Pasquini et al, quoted by Al-Ani et al., 1970 al., 1970).

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Anatomy

Absence of third molar in 7% of cases (1/20) (Festing, 1975b). High incidence of absence of the 3rd. molar, which has been used as a threshold character to study the effects of weak teratogens (Berry and Nickols 1979)

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Drugs

Sensitive to insulin (2/9) but insensitive to histamine (7/9) (Brown, 1965). Long survival on Warfarin (9/12) (Lush and Arnold, 1975). Long sleeping time under hexobarbital anaesthetic (13/15) (Lovell, 1976), long sleeping time under pentobarbitone anaesthetic (18/23), Lovell (1986). Highly susceptible to lung tumour induction by urethane (cf. strain A) (Festing 1980).

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Immunology

Incidence of serum antinuclear factor high (2/17) at 28% (Barnes and Tuffrey, 1967). Low antibody affinity to HSA (7/9) (Petty et al., 1972., 1972).

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Infection

Uniquely resistant among twenty strains tested to infection with diverse strains of pneumotropic and neurotropic influenza viruses. Resistance is due to a dominant autosomal gene, (now designated Mx1) and does not depend on the immune system (Fiske and Klein, 1975; Lindenman et al., 1963., 1963). The Mx1 protein exhibits GTPase activity (Nakayama et al, 1993). The Mx1 protein is inducible with interferon and has been used as a cellular marker in studying the movement of glial cells toward a spinal cord demyelinating lesion (Gout and Dubois-Dalcq, 1993). Mx1 exerts its antiviral activity by interfering with the function of the influenza virus polymerase subunit PB2 (Stranden et al, 1993). The Mx1 gene also confers resistance to the tick-born Thogoto virus (Haller et al, 1995) and the tick-born Dhori virus (Thimme et al, 1995).

Develops a chronic non-healing lesion on infection with Leishmania tropica, the parasite causing cutaneous leishmaniasis (Howard et al 1980)

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Reproduction

Good breeding performance (7/25), colony output 1.2 young per female per week, litter size at weaning 5.7 (12/25) (Festing, 1976a).

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Al-Ani A. T., Tunnicliff G., Rick J. T., and Kerkut G. A. (1970) GABA production, acetylcholinesterase activity and biogenic amine levels in brain for mouse strains differing in spontaneous activity and reactivity. Life Sci. 9, 21-27.

Barnes R. D. and Tuffrey M. (1967) Serum antinuclear factor and the influence of environment in mice. Nature 214, 1136-1138.

Berry C. L. and Nickols C. D. (1979) The effects of aspirin on the development of the mouse 3rd. molar. Arch. Toxicol. 42, 185-190.

Brown A. M. (1965) Pharmacogenetics of the mouse. Lab. Anim. Care 15, 111-118.

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.

Festing M. F. W. (1980) Inbred strains and the factorial experimental design in toxicological screening, in Animal Quality and Models in Biomedical Research. Proceeding of the 7th. ICLAS Symposium, Utrecht (Spiegel A., Erichsen S., and Solleveld H. A., eds), pp. 59-66. Gustav Fischer, Stuttgart.

Fiske R. D. and Klein P. A. (1975) Effect of immunosuppression on the genetic resistance of A2G mice to neurovirulent influenza virus. Infect. Immun. 11, 576-587.

Gout O. and Dubois-Dalcq M. (1993) Directed migration of transplanted glial cells toward a spinal cord demyelinating lesion. International Journal of Developmental Neuroscience 11, 613-623.

Haller O., Frese M., Rost D., Nuttall P. A., and Kochs G. (1995) Tick-borne Thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1. Journal of Virology 69, 2596-2601.

Howard J. G., Hale C., and Chan-Liew W. L. (1980) Immunological regulation of experimental cutaneous leishmaniasis 1. Immunogenetic aspects of susceptibility to Leishmania tropica in mice. Parasite Immunol. 2, 303-314.

Lindenman J., Lane C. A., and Hobson D. (1963) The resistance of A2G mice to myxoviruses. J. Immunol. 90, 942-951.

Lovell D.P. (1986) Variation in pentobarbitone sleeping time in mice. I. strain and sex differences. Lab. Anim. 20, 85-90.

Lush I. E. and Arnold C. J. (1975) High coumarin 7-hydroxylase activity does not protect mice against Warfarin. Heredity 35, 279-281.

Nakayama M., Yazaki K., Kusano A., Nagata K., Hanai N., and Ishihama A. (1993) Structure of mouse Mx1 protein. Molecular assembly and GTP-dependent conformational change. J. Biol. Chem. 268, 15033-15038.

Petty R. E., Steward M. W., and Soothill J. F. (1972) The heterogeneity of antibody affinity in inbred mice and its possible immunopathologic significance. Clin. Exp. Immunol. 12, 231-241.

Stranden A. M., Staeheli P., and Pavlovic J. (1993) Function of the mouse Mx1 protein is inhibited by overexpression of the PB2 protein of influenza virus. Virology 197, 642-651.

Strozik E. and Festing M. F. W. (1981) Whisker trimming in mice. Lab. Anim. 15, 309-312.

Thimme R., Frese M., Kochs G., and Haller O. (1995) Mx1 but not MxA confers resistance against tick-borne Dhori virus in mice. Virology 211, 296-301.

Van den Broek F. A. R., Omitzigt C. M., and Beynen A. C. (1993) Whisker trimming behaviour in A2G mice is not prevented by offering means of withdrawal from it. Lab. Anim. 27, 270-272.

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