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Inbred Strains of Mice: CBA

CBA

Inbr: F90-170 depending on substrain. Agouti. Genet. + . Developed by Strong in 1920 from a cross of a Bagg albino female and a DBA male. Strain CBA was selected for a low mammary tumour incidence and C3H for a high incidence. Now widely distributed, and used as a general-purpose strain. Differences between substrains are probably too large to be accounted for by mutation, and some degree of genetic contamination in the past is probable. The following major substrains are recognised: \par

CBA/Ca or CBA/H

Strong, to Jackson Laboratory, to Haldane and Gruneberg in 1932. To Carter 1947 and Harwell 1954. This substrain used in most British research. \par

CBA/Br

Jackson Laboratory, to Haldane 1932, to Bonser (Leeds) approx. 1933. \par

CBA/CaN

Harwell, to National Institutes of Health in 1966. Carries sex-linked immunological deficit which prevents it from responding to type III pneumococcal polysaccharide. Deficit is expressed on B cells (Gershon and Kondo, 1976; Scher et al., 1976). Do not carry naturally occurring tumour-reactive antibodies commonly found in other strains (Martin and Martin, 1975). \par

CBA/J

Strong, to Andervont 1947, to Jackson Laboratory 1948. Carries gene for retinal degeneration (rd). Skin grafts between CBA/J and CBA/Ca are rejected (Green and Kaufer, 1965). \par

CBA/St

Original strain maintained by Strong. \par

CBA/H-T6

T6 translocation backcrossed to CBA/H by Dr M. F. Lyon. Now homozygous for the marker translocation T(14;15) 6Ca, but otherwise congenic with CBA/H.


Behaviour

Low spontaneous bar-pressing activity (13/14), low tail rattling during aggressive encounters (13/14), high social grooming during aggressive encounters (2/14), low intrastrain aggression (13/14) (Southwick and Clark, 1966, 1968). Low locomotor activity (5/5) (Davis and King, 1967). Low locomotor activity when single (6/6), but intermediate when grouped (4/6) (Davis et al., 1967., 1967). Low spontaneous locomotor activity (2/9) (Nikulina et al 1991). Low shock avoidance learning (9/9) (Bovet et al., 1966., 1966, 1969). High shock avoidance learning in Ca substrain (2/8) but not in J substrain (5/8) (Wahlsten, 1973). High water-escape learning in CBA-T6 (2/6) (Festing, 1973b). Highly susceptible (1/9) to "pinch-induced" catalepsy (excessive freezing), possibly due to a sinlge recessive autosomal gene (Kulikov et al, 1993).


Life-span and spontaneous disease

Life-span intermediate both sexes (J substrain) in conventional conditions (11/22 = 527 days males, 10/22 = 527 days females) (Storer, 1966). Life-span (Ca substrain) short in males (4/17 = 486 days) and long in females (17/17 = 825 days) in SPF fostered conditions. Short life-span of males associated with a high incidence of haemothorax, suggesting a high sensitivity to vitamin K deficiency in SPF conditions (Festing and Blackmore, 1971). \par

High gross tumour incidence (J) (3/22) (Storer, 1966). Overall tumour incidence 29% in males, 55% in females, including lymphoma 6% in males, 15% in females, hepatoma 24% in males, zero in females and mammary tumours 33% in females and zero in males (Smith et al., 1973., 1973). Lung adenomas 2-11% in BrA substrain, leukaemia 4-10% (Muhlbock and Tengbergen, 1971). Resistant to the induction of atherosclerosis by a high-fat and high-cholesterol diet (1/13) (Roberts and Thompson, 1976).

Develop a mild hearing loss with onset late in life (contrast C57BL/6J) (Li, 1992, Willott et al, 1993, Li et al, 1993, Li and Borg, 1993). Do not carry any of the single recessive genes found in BALB/cBy, C57BL/6 and WB/ReJ, causing age-related hearing loss. All three genes are present in DBA/2 (Willott et al, 1995).


Normal physiology and biochemistry

High systolic blood pressure (4/19) (Schlager and Weibust, 1967). Low Na/K ratio in erythrocytes (8/9) and in plasma (9/9) (Waymouth, 1973). High serum ceruloplasmin levels in males of Ca and J substrains (5/26 and 6/26), high level in females of Ca substrain (3/27) but intermediate in J substrain (Meier and MacPike, 1968). Low calcium uptake by the heart (5/5) (Mokler and Iturrian, 1973).

High proportion of the time spent sleeping (2/6), with large percentage of slow-wave sleep (1/6) and low percentage of paradoxical sleep (5/6) (Valatx and Bugat, 1974). Low percentage of paradoxical sleep (7/7) (Pagel et al., 1973., 1973). Low metabolic rate (14/18) according to Storer (1967), but high metabolic rate (2/6) according to Pennycuik (1967). High cell turnover in J substrain as estimated by rapid clearance of DNA-bound radioactivity (2/17) (Heiniger et al., 1972., 1972).

High peripheral nerve conduction velocity (2/6) (Hegmann, 1972). High brain glutamic acid decarboxylase (3/10) (Gaitonde and Festing, 1976). Low hypoxanthine-guanine phosphoribosyl transferase in thalamus (6/7), but high level in hypothalamus (2/7) (Suran, 1973). High brain monoamine oxidase (1/7) and low level of catechol-O-methyltransferase (6/7) activity (Tunnicliff et al., 1973., 1973). Low brain tyrosine hydroxylase activity (5/5) (Ciranello et al., 1972., 1972). Low peptidyl proline hydroxylase activity in mammary gland, foot pad and tumours (5/5) (Cutroneo et al., 1973., 1973). High sensitivity to thyrotropin in J substrain (1/21) (Levy et al., 1965., 1965). High coumarin hydroxylating ability (cf. 4/13) (Lush and Arnold, 1975). High hepatic 3 aminolaevulinic acid synthetase activity after DDC treatment (1/15) (Gross and Hutton, 1971). High porphyrin content in Harderian gland (3/16) (Margolis, 1971). High hind foot pad temperature (1/9) (Shepard and Habas, 1967). Have only about 20% of the maltase (gamma-glucoamylase) activity found in other strains, though there is no evidence for any gross metabolic abnormality resulting from this defect (Quezada-Calvillo et al, 1993).


Anatomy

Large brain weight (17/18 male, 16/18 female) (Storer, 1967). Large forebrain volume (2/9) and neocortex (2/9) (Wimer et al., 1969., 1969). Small brain/body weight ratio (17/20) (Roderick et al., 1973., 1973). Low testes weight (7/8) (Shire and Bartke, 1972). Large kidney/body weight ratio (5/21) (Schlager, 1968). Low thyroid weight (4/5) (Mendoza et al., 1967., 1967). Small heart/body weight ratio (5/5) (Mokler and Iturrian, 1973). Large pituitary (2/6) (Sinha et al., 1975., 1975). Low total leukocyte count (15/18), high erythrocyte count (6/18) (Russell et al., 1951., 1951). Few bristles on foot pads (8/8) (Festing, 1974a). Third molars small and one or more absent in about 18% of individuals (Hummel et al., 1966., 1966).


Drugs

Resistant to urethane-induced lung tumours (Falconer and Bloom, 1962). Susceptible to skin ulceration by DMBA (cf. 13/22) (Thomas et al., 1973., 1973). Susceptible to induction of leukaemia (2/6) and liver tumours (2/6) by neonatally administered DMBA (Flaks, 1968). Susceptible to X-irradiation (27/27) (Roderick, 1963), but resistant to `CNS syndrome' with high doses of X-irradiation (1/5) (Yuhas, 1968). Susceptible to hyperbaric oxygen, showing central nervous system manifestations (11/18) (Hill et al., 1968., 1968). Sensitive to lethal effect of ozone (2/21) (Goldstein et al., 1973., 1973), but resistant (cf 3/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995). Sensitive to teratogenic effect of acetazolamide (1/6) (Green et al., 1973, Hackman and Hurley 1983ey 1983), but resistant to induction of cleft palate in embryos by cortisone (5/5) (Kalter, 1965). Insensitive to insulin (7/9) (Brown, 1965). Long survival on Warfarin (11/12) (Lush and Arnold, 1975). High ED50 to behavioural effects of nicotine (16/19) (Marks et al 1989). Susceptible to weight loss induced by cocaine, but this is attenuated by anisomycin (cf C3H, SJL) (Shimosato et al, 1994). More resistant to acute toxic effects of aflatoxin B-1 than strain C57BL/6 (Almeida et al, 1996).


Immunology

Low lymphocyte phytohaemagglutinin response (35/43) (Heiniger et al., 1975., 1975). Good immune response to low doses of bovine gamma-globulin (cf. 4/8) (Levine and Vaz, 1970). Good splenic PFC immune response to pneumococcal polysaccharide in CBA/H-T6 (3/9), but poor in CBA/J (9/9) and CBA/H (7/9) (Amsbaugh et al., 1972., 1972). Good immune response to ovomucoid, but poor response to ovalbumin (cf. 5/12) (Vaz et al., 1971., 1971). Resistant to induction of antigen-induced arthritis (contrast `most other strains') (Brackertz et al., 1977., 1977). Non-responder to synthetic polypeptide Glu57, Lys38, Ala5 (cf. 4/7) (Pinchuck and Maurer, 1965). Discriminator between `H' and `L' sheep red blood cells (cf. 12/18) (McCarthy and Dutton, 1975). Erythrocytes have a high agglutinability (cf. 14/25) (Rubinstein et al., 1974., 1974). Low responder 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). High natural killer cell response to the immunostimulent 7-allyl-8-oxoguanosine (2/6) (Pope et al, 1994). Diminished expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin A stimulated T lymphoblasts in J substrain (cf 3/6) (Muthing, 1997).


Infection

Resistant to infection by Salmonella typhimurium strain C5 (7/7) (Plant and Glynn, 1974). Susceptible to infection by liver fluke Opisthorchis felineus (2/6) (Zelentsov, 1974). Good plateau harvest of Mycobacterium leprae 8 months after infection (1/9) (Shepard and Habas, 1967). Low immune response to Mycobacterium lepraemurium is associated with an impared macrophage function (Saito and Natori 1985). Resistant to infection by Helicobacter felis with only mild gastritis in the antrum and no atrophy seen over time (cf BALB/c, contrast 4 other strains) (Sakagami et al, 1996). Resistant to induction of diabetes mellitus by encephalomyocarditis virus (cf. 7/14) (Boucher et al., 1975., 1975). Highly susceptible to measles virus (cf. 3/6) (Rager-Zisman et al., 1976., 1976). Ca, H-T6 and N substrains carry no detectable endogenous ecotropic MuLV DNA sequences (Jenkins et al 1982). Administration of cadmium results in a high incidence of activation of latent herpes simplex virus infections. This is not seen in other strains, and does not correlate with cadmium toxicity (Fawl et al, 1996).

J substrain resistant (2/7) to the induction of dental caries due to infection with Streptococcus mutans (Kurihara et al 1991). Resistant (4/4) to murine herpes virus (Kapoor et al 1992). Resistant to intra-vaginally innoculated Neisseria gonorrhoeae (c.f. 5/5) (Johnson et al 1989). Develop severe lesions (2/8) following infection with Candida albicans (Ashman et al, 1993). This correlates with low induction of Candida-specific gamma interferon (Ashman and Bolitho, 1993). CBA/J resistant, with low amylase response to the fungus Paracoccidioides brasiliensis (cf 6/12) (Xidieh et al, 1994).

J substrain is susceptible to several clinical isolates of penicillin-susceptible and resistant strains of Streptococcus pneumoniae, and may be a useful model for evaluating antibiotic efficiencies against this bacterium (Tateda et al, 1996). Resistant to Leishmania major (contrast BALB/c) (Laskay et al, 1995). Ca substrain susceptible to L. major mexicana, and vaccination against the parasite using liposomes with parasite membrane antigens was effective (cf C57BL/6 but contrast C57BL/10) (Lazama-Davila, 1997). Infection with larval Echinococcus multilocularis by transportal injection of hyatid homogenate results in well developed protoscoleces (cf 4/9) (Nakaya et al, 1997).


Reproduction

Good breeding performance (9/25), colony output 1.15 young/female/week, litter size at weaning 5.8(11/25), T6 substrain about equal (Festing 1976a, original data). Intermediate breeding performance (4/8), litter size 5.4, sterility 5.2% (Nagasawa et al., 1973., 1973). Good litter size (1/6 to 3/6, depending on parity), but low proportion of females produce four or more litters (2/6) (Fernandes et al., 1973., 1973). Poor breeding performance in N substrain (21/24) (Hansen et al., 1973., 1973). Low percentage pre-implantation loss of embryos (2/8) (Leonard et al., 1971., 1971). Females have a high rate of fetal resorption when mated with DBA/2 males, but this can be dramatically reduced by immunization with BALB/c, but not DBA/2J spleen cells. This may provide an animal model for the prevention of fetal death by vaccination (Chaouat et al 1985). Maturity of the cytoplasm in oocytes is acquired earlier than in those of the KE or other strains of mice so far studied. (Polanski 1990) \par


Miscellaneous

Recommended host for transplantable rhabdomyosarcoma BW 10139 (Kaliss, 1972). High rate of spontaneous mutations (2/21) (Schlager and Dickie, 1967).


Almeida R. M. A., Correa B., Xavier J. G., Mallozzi M. A. B., Gambale W., and Paula C. R. (1996) Acute effect of aflatoxin B-1 on different inbred mouse strains. Mycopathologia 133, 23-29. \par

Amsbaugh D. F., Hansen C. T., Prescott B., Stashak P. W., Barthold D. R., and Baker P. J. (1972) Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J. Exp. Med. 136, 931-949. \par

Ashman R. B. and Bolitho E. M. (1993) Strain differences in the severity of lesions in murine systemic candidiasis correlate with the production of functional gamma interferon by Candida-activated lymphocytes in vitro. Lymphokine and Cytokine Research 12, 471-476. \par

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

Boucher D. W., Hayashi K., Rosenthal J., and Notkins A. L. (1975) Virus-induced diabetes mellitus. III. Influence of sex and strain of host. J. Infect. Dis. 131, 462-466. \par

Bovet D., Bovet-Nitti F., and Oliverio A. (1966) Effects of nicotine on avoidance conditioning of inbred strains of mice. Psychopharmacologia 10, 1-5. \par

Brackertz D., Mitchell G. F., Vadas M. A., Mackay I. R., and Miller J. F. A. P. (1977) Studies on antigen-induced arthritis in mice. II. Immunological correlates of arthritis susceptibility in mice. J. Immunol. 118, 1639-1644. \par

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Chaouat G., Kolb J.-P., Kiger N., Stanislawski M., and Wegmann T. G. (1985) Immunologic consequences of vaccination against abortion in mice. J. Immunol. 134, 1594-1598. \par

Ciranello R. D., Barchas R., Kessler S., and Barchas J. D. (1972) Catecholamines: strain differences in biosynthetic enzyme activity in mice. Life Sci. 11, 565-572. \par

Cutroneo K. R., Guzman N. A., and Liebelt A. G. (1973) Elevation of peptidylproline hydroxylase activity and collagen synthesis in spontaneous primary mammary cancers of inbred mice. Cancer Res. 32, 2828-2833. \par

Davis W. M. and King W. T. (1967) Pharmacogenetic factor in the convulsive responses of mice to flurothyl. Experientia 23, 214-215. \par

Falconer D. S. and Bloom J. L. (1962) A genetic study of induced lung tumours in mice. Brit. J. Cancer 16, 665-685. \par

Fawl R. L., Gesser R. M., Valyinagi T., and Fraser N. W. (1996) Reactivation of herpes-simplex virus from latently infected mice after administration of cadmium is mouse-strain-dependent. J. Gen. Virol. 77, 2781-2786. \par

Fernandes G., Yunis E. J., and Good R. A. (1973) Reproductive deficiency of NZB male mice. Possibility of a viral basis. Lab. Invest. 29, 278-281. \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

Flaks A. (1968) The susceptibility of various strains of neonatal mice to the carcinogenic effects of 9, 1 0-dimethyl- 1, 2-benzanthracene. Eur. J. Cancer 4, 579-585. \par

Gaitonde M. K. and Festing M. F. W. (1976) Brain glutamic acid decarboxylase and open field activity in ten inbred strains of mice. Brain Res. 103, 617-621. \par

Gershon R. K. and Kondo K. (1976) Deficient production of a thymus- dependent high affinity antibody subset in mice (CBA/N) with an X-linked B lymphocyte defect. J. Immunol. 117, 701-702. \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

Green M. C. and Kaufer K. A. (1965) A test for histocompatibility between sublines of the CBA strain of mice. Transplant. 3, 767-768. \par

Green M. C., Azar C. A., and Maren T. H. (1973) Strain differences in susceptibility to the teratogenic effect of acetazolamide in mice. Teratology 8, 143-145. \par

Gross S. and Hutton J. (1971) Induction of hepatic -aminolaevulinic acid synthetase activity in strains of inbred mice. J. Biol. Chem. 246, 606-614. \par

Hackman R. M. and Hurley L. S. (1983) Interaction of dietary zinc, genetic strain, and acetazolamide in teratogenesis in mice. Teratology 28, 355-368. \par

Hansen C. T., Judge F. J., and Whitney R. A. (1973) Catalog of NIH rodents. National Institutes of Health. DHEW publication (NIH) 74-606, Bethesda. \par

Hegmann J. P. (1972) Physiological function and behavioural genetics. I. Genetic variance for peripheral nerve conduction velocity in mice. Behav. Genet. 2, 55-67. \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

Hill G. B., Osterhout S., and O'Fallon W. M. (1968) Variation in response to hyperbaric oxygen among inbred strains of mice. Proc. Soc. Exp. Biol. Med. 129, 687-689. \par

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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

Johnson A. P., Tuffrey M., and Taylor-Robinson D. (1989) Resistance of mice to genital infection with Neisseria gonorrhoeae. J. Med. Microbiol. 30, 33-36. \par

Kalter H. (1965) Interplay of intrinsic and extrinsic factors, in Teratology (Wilson J. G. and Warkany J., eds) University of Chicago Press, Chicago. \par

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Kawashima I., Nakamura O., and Tai T. (1992) Antibody responses to ganglio-series gangliosides in different strains of inbred mice. Molecular Immunology 29, 625-632. \par

Kulikov A. V., Kozlachkova E. Y., Maslova G. B., and Popova N. K. (1993) Inheritance of predisposition to catalepsy in mice. Behav. Genet. 23, 379-384. \par

Kurihara Y., Naito T., Obayashi K., Hirasawa M., Kurihara Y., and Moriwaki K. (1991) Caries susceptibility in inbred mouse strains and inheritance patterns in F1 and backcross (N2) progeny from strains with high and low caries susceptibility. Caries Res. 25, 341-346. \par

Laskay T., Diefenbach A., Rollinghoff M., and Solbach V. (1995) Early parasite containment is decisive for resistance to Leishmania major infection. Eur. J. Immunol. 25, 2220-2227. \par

Leonard A., Deknudt G., and Linden G. (1971) Ovulation and prenatal losses in different strains of mice. Exp. Anim. (France) 4, 1-6. \par

Levine B. B. and Vaz N. M. (1970) Effect of combinations of inbred strain, antigen and antigen dose on immune responsiveness and reagin production in the mouse. Int. Arch. Allergy 39, 156-171. \par

Levy R. P., McGuire W. L., Shaw R. K., and Bartsch G. E. (1965) Effect of species differences of mice on the bioassay of thyrotropin. Endocrinol. 76, 890-894. \par

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Margolis F. L. (1971) Regulation of porphyrin biosynthesis in the Harderian gland of inbred mouse strains. Arch. Biochem. Biophys. 145, 373-381. \par

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Martin S. E. and Martin W. J. (1975) X chromosome-linked defect of CBA/HN mice in production of tumor-reacting naturally occurring IgM antibodies. J. Immunol. 115, 502-507. \par

McCarthy M. M. and Dutton R. W. (1975) The humoral response of mouse spleen cells to two types of sheep erythrocytes. J. Immunol. 115, 1316-1321. \par

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Mendoza L. A., Hamburg M., and Fuld H. (1967) Differences in thyroid activity in several inbred strains of mice. Anat. Rec. 158, 275-280. \par

Mokler C. M. and Iturrian W. B. (1973) Strain differences in subcellular calcium distribution in striated muscle of the mouse. Proc. Soc. Exp. Biol. Med. 142, 919-923. \par

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Pagel J., Pegram V., Vaughn S., Donaldson P., and Bridgers W. (1973) The relationship of REM sleep with learning in mice. Behav. Biol. 9, 383-388. \par

Pennycuik P. R. (1967) A comparison of the effects of a variety of factors on the metabolic rate of the mouse. Aust. J. Biol. Med. Sci. 45, 331-346. \par

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Pope B. L., Chourmouzis E., MacIntyre J. P., Lee S., and Goodman M. G. (1994) Murine strain variation in the natural killer cell and proliferative responses to the immunostimulatory compound 7-Allyl-8-oxoguanosine: Role of cytokines. Cell. Immunol. 159, 194-210. \par

Quezada-Calvillo R., Senchyna M., and Underdown B. J. (1993) Characterization of intestinal gamma-glucoamylase deficiency in CBA/Ca mice. American Journal of Physiology - Gastrointestinal and Liver Physiology 265, G1150-G1157. \par

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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

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

Shepard C. C. and Habas J. A. (1967) Relation of infection to tissue temperature in mice infected with Mycobacterium marinum and Mycobacterium leprae. J. Bacteriol. 93, 790-796. \par

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Shire J. G. M. and Bartke A. (1972) Strain differences in testicular weight and spermatogenesis with special reference to C57BL/10J and DBA/2J mice. J. Endocrinol. 55, 163-171. \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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