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Inbred Strains of Mice: C57BL

C57BL

Black, a. Origin: Little 1921 from the mating of female 57 with male 52 from Miss Abbie Lathrop's stock. The same cross gave rise to strains C57L and C57BR. Female 58 mated with the same male gave rise to strain C58. C57BL is probably the most widely used of all inbred strains, (substrain C57BL/6 alone accounts for over 14% of occasions on which an inbred strain is used) though in many ways it seems to be atypical of inbred strains of laboratory mice. In contrast to 36 other standard inbred strains, it carries a Y chromosome of Asian Mus musculus origin (c.f. AKR and SWR) (Tucker et al 1992), and a LINE-1 element derived from Mus spretus the frequency of which suggests that up to 6.5% of the genome may be of M. spretus origin (Rikke et al, 1995). A probe designated B6-38 to the pseudoautosomal region of the X and Y chromosome has a characteristic Pst I pattern of fragment sizes which is present only in the C57BL family of strains (Kalcheva et al, 1995).

It usually has a good breeding performance, depending on substrain, and has been used as the genetic background for a large number of congenic strains covering both polymorphic and mutant loci. Four major substrains A, GrFa, 6 and 10 appear to be quite similar, and any differences are consistent with what might be expected from the accumulation of new mutations and a small ammount of residual heterozygosity, though McClive et al (1994) have found that B6 and B10 differ at multiple loci on chrosome 4 including the microsatellite markers D4Mit69, D4Mit71 and D4Mit72. Additional microsatellites which distinguish between B6, B10 and C57BLKS are given by Slingsby et al (1996). The former Ks substrain differs at several loci probably as a result of genetic contamination with a DBA substrain. This has been re-named C57BLKS, and is listed separately. The seven major substrains existing in 1935 are listed below. \par

C57BL/A

Inbr(A) ?+142. Origin. Little to A c1932. Maint. by A. \par

C57BL/An

Little to Andervont 1932. Differs from B6 and B10 at the Ce1 locus. \par

C57BL/GrFa.

Origin: Little to Gruneberg 1932, to Falconer 1947. Most British substrains derived from this stock, though 6 and 10 substrains have been imported more recently. This substrain seems to resemble the 6 rather than the 10 substrain. Maint. by Ola \par

C57BL/KaLwN.

To N 1965 from Lw at F35. Maint. by N. \par

C57BL/Ks see C57BLKS \par

C57BL/6

Inbr (J) 150. Origin: substrains 6 and 10 were separated prior to 1937. This substrain is now probably the most widely used of all inbred strains. Substrain 6 and 10 differ at the H9, Igh2 and Lv loci. Maint. by J,N, Ola. \par

C57BL/10

Inbr (J) 158. Origin: see C57BL/6. Maint. by J. \par

C57BL/10ScSn.

Inbr (J) ? +136. Little to W.L.Russell to J.P.Scott at F26 as a separate substrain. To Snell at F35-36. Behaviour differs from C57BL/10J. Maint. by J,N, Ola. \par

C57BL/10Cr

Carries spontaneous lipopolysaccharide mutation lps which appears to resemble that found in C3H/HeJ (Vogel et al 1981).

C57BL/Ola

Carries a spontaneous mutation, Wlds , causing a marked slowing of axonal degeneration during Wallerian degeneration (Tsao et al, 1994).


Behaviour

Substrain unspecified:

High incidence of tail rattling (1/5) (St. John, 1973). Short latency to attack and eat crickets (2/7) (Butler, 1973). High alcohol (ethanol) preference ratio (1/5) (McClearn, 1965). Short latency to emerge from home cage (1/7), short latency to cross barrier in open-field (1/7), low number of stairs climbed (7/7), low urination (6/7) and defaecation (7/7) (McClearn et al., 1970., 1970). \par

C57BL/6

High alcohol (ethanol) preference (1/4) (Fuller, 1964b), (2/18) (Rodgers, 1966). Achieve blood alcohol levels of 60 mg% when access to alcohol is restricted to 60 mins. per day (Le et al, 1994). Alcohol preference may be associated with strain differences in mesolimbic enkephalin gene expression (Ng et al, 1996). A quasi-congenic QTL introgression strain carrying a low alcohol consumption gene from BALB/c has lower voluntary alcohol consumption than C57BL/6, with 96% of loci in common (Vadasz et al, 1996). Low severity of ethanol withdrawal symptoms compared with DBA/2, possibly associated with differences in neuroactive steriod sensitivity (Finn et al, 1997). Alcohol preference is due to at least two recessive quantitative trait loci that are sex-restricted in expression (Melo et al, 1996).

Low `emotionality' (12/15), high open-field exploration (2/15) (Thompson, 1953). High spontaneous locomotor activity (8/9) (Nikulina et al 1991). Short time of immobility in a forced swimming test (8/9) (Nikulina et al 1991). Low shock-avoidance learning (7/9) (Bovet et al., 1966., 1966, 1969). Low shuttle-box avoidance (5/5), high wheel activity (1/5) (Messeri et al., 1972., 1972). Rapid shock-avoidance learning (2/7) and slow extinction (6/7) (Schlesinger and Wimer, 1967). High shock-avoidance learning (1/8) (Wahlsten, 1973). High radial-arm maze learning (1/3) (Ammassari-Teule et al, 1993).

High locomotor activity (1/5) (Davis and King, 1967). High locomotor activity when grouped (2/6) and single (1/6) (Davis et al., 1967., 1967). Resistant to audiogenic seizures (11/11) (Fuller and Sjursen, 1967). Relatively insensitive to the primary odorant isovaleric acid (contrast seven other strains) and may provide an animal model of specific anosmia (Wysocki et al., 1977., 1977). Low balsa-wood gnawing activity (2/16) Fawdington and Festing (1980). High preference for sweet tasting substances (saccharin, sucrose, dulcin and acesulfame, averaged) (1/26) (Lush 1988). Rejects saline at moderate concentrations (contrast 129) (Beauchamp and Fisher, 1993, Gannon and Contreras, 1995). Feed restriction for nine days failed to cause stereotypic cage cover climbing (contrast DBA/2) (Cabib and Bonaventira, 1997). \par

C57BL/10

High open-field activity (3/15) (Thompson, 1953). High alcohol preference (6/18) (Rodgers, 1966). Good water escape learning (1/6) (Festing 1973b). Good performance in food-seeking task (1/6) (Henderson, 1970). Insensitive to the odour of isovaleric acid (see C57BL/6). High preference for sweet tasting substances (saccharin, sucrose, dulcin and acesulfame, averaged) (4/26) (Lush 1988).


Life-span and spontaneous disease

Substrain unspecified:

Mammary tumours less than 1% (Heston and Vlahakis, 1971). Lung adenomas 0-9% in LiA substrain (Mühlbock and Tengbergen, 1971). Zero incidence of mammary tumours at 2 years (cf. 3/7) (Bentvelzen et al., 1970., 1970). \par

Mean life-span 800 days in males and 750 days in females according to Rowlatt et al. (1976), who also give details of pathology in a large aging colony of C57BL/Icrf-at mice. Hyperphalangy and polydactyly occur with a low incidence in all C57BL strains and substrains (Dagg, 1966). Hydrocephalus 4.1% (Mori, 1968). Type B reticulum cell neoplasms 75% at about 20 weeks in HeDe substrain (Dunn and Deringer, 1968). \par

C57BL/Ka

Median life-span 23 months in males. Main autopsy findings include reticulum cell sarcoma type B (29%), testes interstitial tumour (13%), thyroid follicular adenoma (9%), unclassified lymphoreticular tumours (9%). Nine other tumour types found. Non-neoplastic lesions include amyloid (83%), Sendai virus pneumonia (20%), periarteritis nodosa (16%), mesenteric disease (10%). Several other lesions noted. (Zurcher et al., 1975). About 50% of mice develop homogeneous immunoglobulins resembling idiopathic paraproteinaemia in man by 24 months (Radl and Hollander, 1974). \par

C57BL/Fa

Long life-span in males (14/17 = 645 days), but intermediate in females (5/17 = 580 days) in SPF fostered conditions (Festing and Blackmore, 1971). Hydronephrosis 0.5% in females, 1.5% in males (Taylor and Fraser, 1973). \par

C57BL/6

Primary lung tumours 1% in males, 3% in breeding females and zero in virgin females. Lymphatic leukaemia less than 2%, mammary adenocarcinomas less than 1% (Hoag, 1963). Leukaemia 7% (Myers et al., 1970., 1970). Rare "lipomatous" hamartomas or choristomas have been noted (Adkison et al 1991).

Susceptible to the development of atheromatous lesions on wall of aorta after 20 weeks on a high-fat diet (Thompson, 1968; Roberts and Thompson, 1976). Develop fatty streak-like lesions in the valve sinus region of the ascending aorta after 10-20 weeks on a diet enriched in saturated fat and cholesterol. After a further 15 weeks fibro-fatty lesions with many of the characteristics of human atheromatous plaques are found (Stewart-Phillips and Lough 1991). Exhibit aortic cartilaginous metaplasia (contrast C3H) (Qiao et al, 1995). Susceptible to diet-induced aortic fatty streak lesions which correlates with a low level of paroxinase mRNA (contrast C3H) (Shih et al, 1996).

Develops non-insulin-dependent diabetes mellitus and hypertension when fed a high fat-high simple carbohydrate diet, whereas A/J mice do not (Mills et al 1993). Susceptible to the development of atherosclerosis on a semi-synthetic high fat diet (1/9) (Nishina 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 simple carbohydrate diet for five months induced hyperglycemia, hyperinsulinemia and hypercholesterolemia and non-insulin-dependent diabetes mellitus which appeared to be associated with the metabolic characteristics of visceral fat (Rebuffe-Scrive et al, 1993). Gain more weight on high fat diets without consuming more calories than A/J mice and develop adipocyte hyperplasia. However, animals fed a low fat, high sucrose diet were leaner than those fed a high-complex-carbohydrate diet. These results suggest that genetic differences in metabolic response to fat is more important in the development of obesity and diabetes than caloric intake (Surwit et al, 1995). Loci on chromosomes 1, 3, 5 and 11 are associated with variation in high density lipoprotein levels with coordinate expression of cholesterol-7-alpha hydroxylase in a cross involving atherosclerosis resistant C3H/HeJ mice (Machleder et al, 1997). Hepatic stearoyl CoA desaturase mRNA levels significantly elevated compared with atherosclerosis-resistant BALB/c mice, and was reduced in mice fed a high fat diet (Park et al, 1997).

Congenital abnormalities 10%, including eye defects, polydactyly and otocephaly (Kalter, 1968). Microphthalmia and anophthalmia 8-20% and hydrocephalus 1-3% (Dagg, 1966). Occular defects appear to be due to defects in development of the lens (Robinson et al, 1993).

Develop spontaneous auditory degeneration with onset during young adulthood, with enhanced susceptibility to acoustic injury and delayed effects of toluene (contrast CBA/Ca) (Li, 1992, Willott et al, 1993, Li et al, 1993, Li and Borg, 1993). This is associated with early hair cell changes including bent and fused stereocillia, bulging of the cuticle plates, hair cell loss and swelling of affected dendrites (Hultcrantz and Li, 1993). Carry a single recessive gene different from that found in BALB/cBy and WB/ReJ, causing age-related hearing loss (Willott et al, 1995). Hearing loss is caused by degeneration of the organ of Corti, originating in the basal, high frequency region and then proceeding apically over time. This results in a severe sensorineural hearing loss by 14 months of age (Walton et al, 1995). More susceptible to noise-induced hearing loss than CBA/J (Erway et al, 1996).

Life-span above average in both sexes in conventional conditions (17/22 = 676 days in males, 18/22 = 692 days in females) (Storer, 1966). Life-span 827 _ 34 days in males, 818 _ 21 days in females (Goodrick, 1975). Life-span 878 _ 10 days in males and 794 _ 6 days in females (Kunstyr and Leuenberger, 1975). Median life-span 600 days (Curtis, 1971). Gross tumour incidence 70%, maximum life-span about 1200 days in SPF conditions (Mewissen, 1971). \par

Dermatitis with intense pruritis leading to self-mutilation and death, and sometimes associated with the mite Myobia musculi appears to be more severe in this strain than others (Csiza and McMartin, 1976). Impaired axonal regeneration involving multiple genetic loci (Lu et al, 1994) \par

C57BL/10

Long life-span (826_29 days in males, 693_31 days in females). Overall tumour incidence 33% in males and 31% in females, most of which is due to lymphoma (31% in males, 29% in females) (Smith et al., 1973., 1973). Microphthalmia and anophthalmia 8-20% and hydrocephalus 1-3% (Dagg, 1966). Dermatitis leading to self-mutilation as described in C57BL/6 is also common in this substrain. Incidence may reach 4% (Sparrow, personal communication).


Normal physiology and biochemistry

Substrain other than /6 or /10

High thyroid activity (1/5) (Van Heyningen, 1961). Mammary gland insensitive to oestradiol and progesterone (6/7) (Singh et al., 1970., 1970). Low brain aromatic L- amino acid decarboxylase (5/5) and low acetylcholinesterase activity (5/5) (Pryor et al., 1966., 1966). Blood catalase has a low specific activity (6/7) (Magdon, 1962). \par

Low hind foot pad (9/9) but high (1/9) tail temperature (Shepard and Habas, 1967). High serum calcium (2/6) (Barrett et al., 1975., 1975). Low erythrocyte catalase (12/18 to 17/18, depending on substrain) (Hoffman and Rechcigl, 1971). High basal level of serum prolactin (1/6) (Sinha et al., 1975., 1975). Resistant to dietary induction of obesity (Fenton and Dowling, 1953). High level of alpha-fetoprotein in plasma at 7 days (1/6) (Adinolfi et al 1990). \par

C57BL/6

Low plasma cholesterol at 12 and 24 weeks (8/8) (Weibust, 1973). Low plasma triglyceride levels (1/11 in By and 3/11 in J substrains) and low plasma cholesterol (2/11 in By and 4/11 in J substrains) (Jiao et al 1990). Low serum ceruloplasmin levels in males (24/26) but intermediate in females (Meier and MacPike, 1968). High blood sugar (3/12) (Nishimura, 1969). Low serum cholesterol (5/5) in C57BL/6-ata (Bruell et al., 1962., 1962). Arterial blood has a low pH (10/10) (Bernstein, 1966). Low concentration of prostaglandin F in epididymis (6/6) (Badr, 1975). High liver tyrosine aminotransferase in fasted mice (3/10) but low in C57BL/6-ob (10/10) (Blake, 1970). Low brain L-glutamic acid decarboxylase (GAD) (7/7) and acetylcholinesterase activity (7/7) but high catechol-O-methyltransferase activity (2/7) (Tunnicliff et al., 1973., 1973). Low calcium uptake by the heart (4/5) (Mokler and Iturrian, 1973). Low sensitivity to thyrotropin (20/21) (Levy et al., 1965., 1965). High brain sulphatide (1/5) (Sampugna et al., 1975., 1975). High hepatic benz (alpha) pyrene hydroxylase activity (1/6) (Kodama and Bock, 1970). Low hepatic delta-aminolaevulinate dehydratase activity (8/8) (Doyle and Schimke, 1969). High aldehyde dehydrogenase and alcohol dehydrogenase activity compared with DBA/2 (Sheppard et al., 1968., 1968). High metabolism of 131I with low 48 h retention (1/6) (Chai et al., 1957., 1957). High liver arylsulphatase activity (1/12) (Daniel, 1976). Low porphyrin content of Harderian gland (16/16) (Margolis, 1971). Low hepatic urokinase activity (4/6 to 6/6) but high hepatic histidine ammonia-lyase activity (1/6 to 2/6 in two substrains) (Hanford et al., 1974., 1974). Low basal levels of kidney catalase (4/4), superoxide dismutase (4/4) and renal glutathione reductase (4/4) (Misra et al 1991). Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase and uroporphyria in C57BL/10ScSn but not DBA/2 mice. This was not correlated with the Ah locus in a study involving 12 mouse strains (Smith and Francis, 1993). Low levels of apoA-IV messenger RNA in liver compared with 129/J (Reue et al, 1993)

Low susceptibility to audiogenic seizures (6/6) (Deckard et al., 1976., 1976). Long tau DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness (12/12) (Schwartz and Zimmerman 1990)

Has defective secretory group II phospholipase A2 gene (cf strains 129/Sv and B10.RIII) (Kennedy et al, 1995).

Susceptible to severe hypercapnia with hypoxia assessed by elevated minute ventilation rate (1/8) (Tankersley et al, 1994). Has a rapid and shallow breathing pattern phenotype (contrast C3H) (Tankersley et al, 1997). Susceptible (1/7) to cerebral ischemia following bilateral carotid occlusion with 90% of mice showing typical neuological signs such as torsion of the neck and rolling fits with selective neuronal death in the hippocampus and caudoputamen after 20 minutes of ischemia (Yang et al, 1997).

C57BL/10

Low plasma testosterone level (4/5) (Hampl et al., 1971., 1971). High Na/K ratio in erythrocytes (3/9) and plasma (2/9) (Waymouth, 1973). Low serum ceruloplasmin levels in males (25/26) but intermediate in females (Meier and MacPike, 1968). Low systolic blood pressure (18/19) (Schlager and Weibust, 1967). Low brain glutamic acid decarboxylase in B10.BR (10/10) and ScSn substrains (9/10) (Gaitonde and Festing, 1976). Resistant to electroconvulsive seizures (6/6) (Deckard et al., 1976., 1976). Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase and uroporphyria in C57BL/10ScSn but not DBA/2 mice. This was not correlated with the Ah locus in a study involving 12 mouse strains (Smith and Francis, 1993).


Anatomy

Substrain unspecified

Low proportion of basophilic cells in adenohypophysis (5/5) (Keramidas and Symeonidis, 1973). \par

C57BL/6

Small kidney/body weight ratio (19/21) (Schlager, 1968). Large thyroid (1/5) (Mendoza et al., 1967., 1967). High total leukocyte count (2/18), low erythrocyte count (14/18) (Russell et al., 1951., 1951). Small hippocampus (9/9) (Wimer et al., 1969., 1969). Accessory spleens in about 32% of mice (2/9) and low number of Peyer's patches (7/7) (Hummel et al., 1966., 1966). Higher bone mass than A/J (Kaye and Kusy, 1995). Low number of haematopoetic stem cells in bone marrow (contrast DBA/2) (Muller-Sieburg and Riblet, 1996).

Less susceptible to the development of micronuclei than BALB/c following treatment with clastogenic base analogues and nucleosides (Sato et al, 1993). High level of spontaneous sister chromatid exchange (4/4) (Nishi et al, 1993). A detailed staging of these mice between gestation days 11 and 13 (Theiler's stages 18 and 21) has been published by Miyake et al, (1996). Hematopoetic stem-cell pool 11-fold lower than in DBA/2. This is largely due to loci on chromosome 1 (Mullersieburg and Riblet, 1996). Low bone density of femur (11/11) (Beamer et al, 1996). The timing of onset and duration of condensation and onset of matrix formation of first arch cartilages has been described by Miyake et al (1996a). A detailed staging table to facilitate study of cranial skeletal development every 2hrs. between days 11 and 13 of gestation has also been described (Miyake et al, 1996b)

C57BL/10

Small kidney/body weight ratio (21/21) (Schlager, 1968). High number of bristles on foot pad (1/8 to 3/8 in three congenic lines) (Festing, 1976a). High yield of peritoneal exudate cells (1/5) with a high percentage of macrophages (1/5), low percentage of lymphocytes (5/5) and high granulocytes (1/5) (Schwartz et al., 1975., 1975).


Drugs

Substrain unspecified

Resistant to induction of adenocarcinomas of the colon by 1, 2-dimethylhydrazine (cf. 2/4) (Evans et al., 1974., 1974). Resistant to induction of pulmonary tumours (6/6) and leukaemia (5/6) by neonatal administration of DMBA (Flaks, 1968). Susceptible to the induction of pulmonary fibrosis by bleomycin (contrast C3Hf/Kam) (Haston et al, 1996) and irradiation, though the sensitivity of lung fibroblasts to irradiation in-vitro does not correlate with in-vivo sensitivity (Dileto and Travis, 1996).

Sensitive to the development of uterine tumours following treatment with DMBA at 4-weeks of age (cf 3/6) (Tsubura et al, 1993). Resistant to induction of mammary tumours by urethane (7/7) (Bentvelzen et al., 1970., 1970). Pituitary adenoma induced in most mice by oestrogens (Heston, 1963). Resistant to skin tumour induction by methylcholanthrene (5/5) (Andervont and Edgcomb, 1956). Susceptible to fibrosarcoma induction by methylcholanthrene (4/15 males, 3/15 females) (Strong, 1952).

Resistant to chloroform toxicity (cf. 5/9) (Deringer et al., 1953., 1953). Resistant to induction of cleft palate by cortisone (4/5) (Kalter, 1965). \par

Resistant to lethal effects of ozone (22/22) (Goldstein et al., 1973., 1973). Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7) (Evans et al., 1977., 1977). \par

C57BL/Fa

Resistant to induction of lung tumours by urethane (6/6) (Falconer and Bloom, 1962). Insensitive to insulin (8/9), sensitive to histamine (2/9) (Brown, 1965). \par

C57BL/6

Susceptible to skin ulceration by DMBA (cf. 13/22) (Thomas et al., 1973., 1973). Susceptible to induction of subcutaneous tumours by 3-methylcholanthrene (3/14) (Kouri et al., 1973., 1973), (1/12) (Whitmire et al., 1971., 1971). High incidence of lymphomas after methylcholanthrene administration by gavage (2/5) (Akamatsu and Barton, 1974). Susceptible to toxic effects of DMBA (6/6) (Schmid et al., 1966., 1966). Pre-treatment with beta-naphthoflavone 48 hr. before administration of N-nitrosoethylurea (ENU), once weekly for 4 weeks caused a significant doubling in the number of lung tumor bearers (contrast 4 strains) (Anderson et al 1990). Phenobarbitone in the diet to give an intake of 85mg/kg per day resulted in 4% of animals developing basophilic nodules by 91 weeks of age (contrast 70% in C3H/He), but no increase in liver carcinomas (Evans et al, 1992). However, there was a two-fold lower level of DNA synthesis in C57BL/6 mice relative to C3H mice after partial hepatactomy, though partial hepatectomy is a tumour promoter in C57BL/6 but not in C3H mice (Bennett et al, 1995).

Sensitive to teratogenic effects of acetazolamide (2/6) (Green et al., 1973., 1973). Resistant to teratogenic effect (cleft palate) by cortisone acetate (2/6) (Kalter 1981). Hepatic epoxide hydrase activity induced by pentobarbital i.p. (cf. 4/7) (Oesch et al., 1973., 1973). Resistant to teratogenic effects of cortisone acetate (4/4) (Dostal and Jelinek, 1973). Resistant to lethal effects of ozone (16/21) (Goldstein et al., 1973., 1973), but susceptible (cf 5/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995) and to airway inflammation (contrast C3H/He) (Kleeberger et al, 1993). Susceptible to ozone-induced lung inflammation, which is exacerbated by vitamin A deficiency (Paquette et al, 1996). High incidence of convulsions induced by flurothyl (1/5) (Davis and King, 1967). Susceptible to hyperbaric oxygen (4/18) (Hill et al., 1968., 1968). Resistant to chloroform toxicity (cf. 5/9) (Hill et al., 1975; Deringer et al., 1953 al., 1953). Resistant to toxic effects of isoniazid (2/10) (Taylor 1976b). Sensitive, as judged by eosinophil response, to cortisone acetate (cf. 3/6) (Wragg and Speirs, 1952). High (89%) ovulatory response to 3 I.U. of PMS in immature mice (2/6), but only a 56% response to 7 I.U. No facilitation by exposure to males at these doses (Zarrow et al., 1971., 1971). High locomotor activity after treatment with D-amphetamine (1/6) (Babbini et al., 1974., 1974). Nicotine increases learning ability (1/9) (Bovet et al., 1966., 1966). Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7) (Evans et al., 1977., 1977). Low ED50 to behavioural effects of nicotine (3/19) (Marks et al 1989). High self-selection of nicotine (1/6) which is inversely correlated with sensitivity to nicotine-induced seizures (Robinson et al, 1996).

Low bronchial reactivity (6/6) to methacholine and serotonin (Konno et al 1993). Resistant (6/8) to daunomycin-induced nephorsis (Kimura et al 1993). Low (10/10) neural sensitivity to pentylenetetrazol convulsions (Kosobud et al 1992). Susceptible to biliary tract injury following oral dosing with 500 micrograms of the fungal toxin sporidesmin (1/4) (Bhathal et al 1990). Low histamine release from peritoneal mast cells induced by compound 48/80, a calcium dependent histamine releaser ( c.f. 5/8) (Toda et al 1989). Low histamine release from peritoneal mast cells induced by Ca2+ ionophore A23187 ( c.f. 1/8, contrast BALB/c, C3H/He, DBA/2 etc.) (Toda 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 AKR, unlike DBA/2) (Otterness and Weinshilboum 1987a,b). More sensitive to acute toxic effects of aflatoxin B-1 than strains CBA/J or BALB/c (Almeida et al, 1996).

Airways hyporeactive to acetylcholine (c.f. 3/7) (Zhang et al, 1995). High voluntary comsumption of morphine in two-bottle choice situation (1/15) (Belknap et al, 1993). Estrogen induces an increase in VLDL and LDL-cholesterol (like C57L, contrast BALB/c and C3H) (Srivastava, 1995). Nine-fold higher ED50 for haloperidol-induced catalepsy than DBA/2, but this is not associated with numbers of cholinergic neurons (Dains et al, 1996). Accumulates three to five-fold lower levels of mercury in liver and blood than DBA/2 or A.SW after 4 weeks exposure to mercuric chloride, but higher levels in spleen following 8-12 weeks of exposure (Griem et al, 1997).

C57BL/10

Nicotine decreases shock-avoidance learning (8/9) (Bovet et al., 1966., 1966). Low ED50 to behavioural effects of nicotine (1/19) (Marks et al 1989). Congenic line B10.BR susceptible to induction of subcutaneous tumours by 3-methylcholanthrene (Kouri et al., 1973., 1973).


Immunology

Substrain unspecified

Poor immune response to low levels of bovine gamma-globulin (cf. 4/8) (Levine and Vaz, 1970). Poor primary immune response to bovine serum albumin (6/6) (James and Milne, 1972). Poor primary immune response to sheep erythrocytes (3/6 to 6/6, depending on test and dose) (Ghaffar and James, 1973). Poor immune response to Vi antigen (cf. 3/5) (Gaines et al., 1965., 1965). Low antibody affinity (7/7) and small quantity of antibody production (6/7) (Alpers et al., 1972., 1972). Low antibody affinity to HSA (9/9) (Petty et al., 1972., 1972). \par

C57BL/Fa

Serum anti-nuclear factor in 12% of animals tested (5/17) (Barnes and Tuffrey, 1967). Good primary immune response to bacteriophage fd (2/7) (Kolsch et al., 1971). \par

C57BL/6

High susceptibility to induction of amyloid by casein (1/6) (Willerson et al., 1969., 1969). Poor immune response to type III pneumococcal polysaccharide (4/5) (Braley and Freeman, 1971). Poor immune response to synthetic double- stranded RNA (6/7) (Steinberg et al., 1971., 1971). Good immune response to cholera A and B antigens (2/8) (Cerny et al., 1971., 1971). Resistant to induction of anaphylactic shock by ovalbumin (cf. 6/13) (Tanioka and Esaki, 1971). Rapid rejection of about 76% of male skin isografts by females by 25 days (1/10) (Gasser and Silvers, 1971). Poor immune response to GAT (random terpolymer of Glu60, Ala30, Tyr10) (9/10) (Dorf et al., 1974., 1974). Good immune response to Salmonella senftenberg (1/5) and S. anatum (2/5) lipopolysaccharide (Di Pauli, 1972). Non-responder to synthetic polypeptide Glu57, Lys38, Ala5 (cf. 4/7) (Pinchuck and Maurer, 1965). High sporadic occurrence of natural haemagglutinins to sheep red blood cells (Brooke, 1965). Discriminator between `H' and `L' sheep erythrocytes (cf. 12/18) (McCarthy and Dutton, 1975). Poor immune response to Pro-Gly-Pro-ovalbumin (7/7) and (Pro66, Gly34)n (6/7) but good immune response to (Pro-Gly-Pro)n (1/17) (Fuchs et al., 1974., 1974). High (2/6) PHA- stimulated lymphocyte blastogenic response (Hellman and Fowler, 1972). Erythrocytes have low agglutinability (cf. 11/25) (Rubinstein et al., 1974., 1974). High immune response to ferritin in B6-Tla (2/16) (Young et al., 1976., 1976). Low responder to dextran (cf. 6/10) (Blomberg et al., 1972., 1972). Low responder to E. coli ß-D-galactosidase, with "memory" developing in absence of antibody formation (de Macario and Macario 1980). Precipitating and skin sensitising antibodies have slow electrophoretic mobility (6/6) (Fahey, 1965). Resistant to anaphylactic shock (Treadwell, 1969). Susceptible (1/5) to induction of autoimmune prostatisis (contrast BALB/c) (Keetch et al, 1994). High expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin A stimulated T lymphoblasts (cf 3/6) (Muthing, 1997).

Anti-BPO IgE monoclonal antibody produced potent systemic sensitization sufficient for provocation of lethal shock in most aged (6 to 10 months) mice (c.f. 3/8) (Harada et al 1991). Susceptible to immunosuppression of contact hypersensitivity by ultraviolet B light (cf 3/18) (Noonan and Hoffman, 1994). \par

C57BL/10

High lymphocyte phytohaemagglutinin response (10/43) (Heiniger et al., 1975., 1975). Rejection of 70% of male skin isografts by females by 25 days (2/10) (Gasser and Silvers, 1971). Poor immune response to ovomucoid, but good immune response to ovalbumin (cf. 6/12) (Vaz et al., 1971., 1971). Poor immune response to DNP-keyhole limpet haemocyanin (10/11) (Borel and Kilham, 1974). Non-responder to synthetic polypeptide Glu57, Lys58, Ala5 (cf. 4/7) (Pinchuck and Maurer, 1965). Low antibody affinity (6/7) and small quantity of antibody produced (7/7) in B10.D2-n (Alpers et al., 1972., 1972). Discriminator between `H' and `L' sheep erythrocytes (cf. 12/18). Also in B10.BR and B10.D2-n (McCarthy and Dutton, 1975). Low IgM antibody response to sheep red blood cells compared with A/J (Vetvicka et al, 1993). Resistant to induction of passive cutaneous anaphylaxis (IgG1- and IgE- mediated) (12/12) (De Souza et al., 1974., 1974). Erythrocytes have low agglutinability (cf. 11/25) (Rubinstein et al., 1974., 1974). High immune response to ferritin in B10 (4/16) and congenic lines B10.M (1/16), B10.D2 (3/I6), B10.BR (5/16) and B10.A (6/16) (Young et al., 1976., 1976). Susceptible to immunosuppression of contact hypersensitivity by ultraviolet B light (cf 3/18) (Noonan and Hoffman, 1994). High neutrophil response to thioglycolate broth and killed bacteria (contrast BALB/c) (Marley et al, 1994). Moderate susceptibility to experimental allergic encephalomyelitis with long (1/10) duration (Lindsey, 1996).


Infection

Substrain unspecified

Resistant to oncogenic effects of polyoma virus given at birth (Law, 1966a). Resistant to Mycobacterium marinum (2/9) and poor plateau harvest of M. leprae 8 months after infection (9/9) (Shepard and Habas, 1967). \par

C57BL/Fa

Highly susceptible to infection by Salmonella typhimurium strain C5 (2/7) (Plant and Glynn, 1974). \par

C57BL/6

Develops a slowly progressing parasitosis ("low responder") after infection with the Cornell strain of Toxoplasma gondii (Macario et al 1980). Did not support sustained growth of six strains of Leishmania mexicana mexicana (contrast BALB/c) (Monroy-Ostria et al, 1994). Resistant to Leishmania major (contrast BALB/c) (Laskay et al, 1995, Scott et al, 1996). Susceptible to L. major mexicana, and vaccination against the parasite using liposomes with parasite membrane antigens was effective (cf CBA/Ca but contrast C57BL/10) (Lazama-Davila, 1997).

Susceptible to Salmonella typhimurium strain C5 (1/5) (Robson and Vas, 1972). 100-fold more resistant to Listeria monocytogenes than A/J when measured by median lethal dose (Sadarangani et al 1980). This seems to be associated with increased levels of gamma interferon and granulocyte-macrophage colony stimulating factor compared with susceptible A/J mice (Iizawa et al, 1993). Resistant to Mycoplasma fermentens (6/6) (Gabridge et al., 1972., 1972). Resistant to Mycoplasma pulmonis infection (cf 4/16) (Cartner et al, 1996).Resistant to infection by Mycobacterium marinum (6/6) (Yamamoto et al 1991). Resistant to infection by liver fluke Opisthorchis felineus (6/6) (Zelentsov, 1974). Resistant (1/4) to infection with the helminth worm Angiostrongylus costaricennsis (Ishii and Sano 1989). Relatively susceptible to infection with Helicobacter felis (contrast C57BL/6) (Mohammadi et al, 1996). Susceptibile to infection by Helicobacter felis with moderate to severe chronic active gastritis in the body of the stomach, which increased over time (cf 4/6) (Sakagami et al, 1996). H. felis induces hypertropic gastropathy (Fox et al, 1996).

Highly resistant to the mammary tumour virus which is thought not to be carried by the strain (Murray and Little, 1967). Resistant to Herpes simplex virus (2/11) (Lopez, 1975). Resistant to herpes simplex virus-1 (contrast BALB/c) (Brenner et al, 1994).. Susceptible to mouse hepatitis virus type 3 infection (cf. 5/14) (Le Prevost et al., 1975., 1975). Develops antibodies to mouse hepatitis virus which can be reliably detected by the complement fixation test, in contrast to five other strains (Kagiyama et al 1991). Low mortality in a natural epizootic of ectromelia (7/8) (Briody, 1966). High expression of RNA tumour virus group-specific antigen in some substrains (1/8) but low in others (7/8) (Whitmire and Salerno, 1972). Resistant to development of leukaemia on infection by Friend virus (cf. 2/11) (Dietz and Rich, 1972). Resistant to diabetogenic effects of encephalomyocarditis virus, but treatment with carrageenan to compromise macrophage function makes the mice susceptible (Hirasawa et al, 1995). Susceptible to measles virus induced encephalitis, which correlates with a high cytotoxic T-lymphocyte response (like C3H, contrast BALB/c) (Niewiesk et al, 1993). Resistant to the development of tumours following inoculation with polyoma virus (Freund et al, 1992).

Resistant (6/7) to the development of chronic Chagas' cardiomyopathy in postacute Trypanosoma cruzi infection (Rowland et al 1992). Resistant to infection with Trypanosoma congolense with an initial peak of parasitemia on day 6, followed by rapid apparent clearance in an average of 3 days (contrast BLAB/c) (Ogunremi and Tabel, 1995). Infection with larval Echinococcus multilocularis by transportal injection of hyatid homogenate results in a multivesiculation form of hyatid development (cf 4/9) (Nakaya et al, 1997). \par

Resistant to tumorigenesis induced by polymoa virus (1/9), in contrast with C3H/Bi (Freund et al 1992). Susceptible to mouse adenovirus type 1 which causes a fatal hemorrhagic encephalomyelitis (contrast BALB/c) (Guida et al, 1995).

Less susceptible to Streptococcus suis type 2 including the type strain, two isolates from meningitis in pigs and two isolates from tonsils of clinically healthy pigs (c.f. 3/5) (Kataoka et al 1991). Resistant to carditis on infection with Lyme borreliosis (Borrelia burgdorferi) (contrast C3H, SWR, BALB/c) (Barthold et al 1990). Thymectomized C57BL/6 mice that were intravenously infused with monoclonal antibody to selectively deplete CD4+ T cells are susceptible to disseminated Mycobacterium avium infection. The increased susceptibility is comparable to that of C57BL/6-bg. The course of such infections can be markedly restrained and in some cases the infections can be sterilized by treatment over a 120-day period with the antimycobacterial agent rifabutin (Furney et al 1990). Susceptible to infection with M. avium strains 101 and 2-151, and can be used to test anti-mycobacterial agents (Furney et al, 1995). Susceptible to infection with M. paratuberculosis (contrast C3H/HeJ) (Tanaka et al, 1994). Resistant to infection with Yersinia enterocolitica associate with a good interferon gamma response (contrast BALB/c) (Autenrieth et al, 1994).

Susceptible, with high amylase response to the fungus Paracoccidioides brasiliensis (cf 6/12) (Xidieh et al, 1994)

Mouse mammary tumor proviral loci have been identified by Lee and Eicher (1990). Resistant (1/10) to infection with Ehrlichia risticii (Williams and Timoney, 1994). Highly susceptible to Plasmodium berghei with all mice developing erythrocytic infection following intravenous injection of 50 sporozoites. The same level of infection could only be established in BALB/c with 10,000 sporozoites (Scheller et al, 1994). Infection with P. berghei results in low blood parasitemia and death with neuological symptoms within 8-10 days, in contrast with the more resistant BALB/c (Moumaris et al (1995). Resistant to chronic weakness and inflammation following infection with Tucon strain of coxsackie virus B1, in contrast with C57BL/10 and B10 congenic strains (Tam and Messner, 1996).

C57BL/10

Congenic line B10.D2-n is highly susceptible to infection by Salmonella typhimurium strain C5 (3/7) (Plant and Glynn, 1974). Resistant to Herpes simplex virus (2/Il) (Lopez, 1975). B10.D2-o is susceptible to mouse hepatitis virus type 3 infection (cf. 5/14) (Le Prevost et al., 1975., 1975). Slow immunological expulsion of Trichinella spiralis worms (Wakelin and Donachie 1980). Following administration of murine cytomegalovirus, C57BL/10 and B10.BR mice developed myocarditis after neonatal infection, but inflammation resolved rapidly after adult infection and age-related cardiopathy was correspondingly mild. (contrast BALB/c, C3H) (Price et al 1991). Resistant to infection with the helminth Mesocestoides corti (contrast SJL, NIH) (Lammas et al 1990). Resistant (2/10) to infection with Ehrlichia risticii (Williams and Timoney, 1994). Susceptible to chronic weakness and inflammation following infection with Tucon strain of coxsackie virus B1, in contrast with C57BL/6 (Tam and Messner, 1996). Resistant to Mycoplasma pulmonis infection (cf 4/16) (Cartner et al, 1996). Infection with larval Echinococcus multilocularis by transportal injection of hyatid homogenate results in a multivesiculation form of hyatid development (cf 4/9) (Nakaya et al, 1997). Susceptible to L. major mexicana, but vaccination against the parasite using liposomes with parasite membrane antigens was not effective (contrast CBA/Ca and C57BL/6) (Lazama-Davila, 1997). \par


Reproduction

C57BL/Fa

Poor reproductive performance (25/25) with only 3 young weaned per litter and 0.4 young per female/week (Festing, 1976a). \par

C57BL/Ka

Good breeding performance, 2.2 young/female/month (6/24) (Hansen et al., 1973., 1973). \par

C57BL/6

Good reproductive performance (3/8). Litter size 6.2 _ 0.2, sterility 8% (Nagasawa et al., 1973., 1973). Large litter size (1/6), mean 6.2 (Verley et al., 1967., 1967). Good breeding performance, 2.5 young/female/month (2/24) (Hansen et al., 1973., 1973). Has longer and more regular oestrus cycles than DBA/2 and C3H/HeJ (Nelson et al 1992). Late opening of vagina and first cornification (3/3), but early onset of cyclicity compared with C3H (Nelson et al 1990).

Mice carrying the Y-chromosome from Mus musculus domesticus from Tirano (Italy) or M.m. poschiavinus from Poschiavo (Switzerland) fail to develop normal testes but instead develop ovaries and ovotestes. Some hermaphroditic males become fertile, but the XY females lack normal gonadal steroids and can not carry pregnancy to term. There is delayed expression of IGF-I which may be responsible for the low setroid expression (Villapandofierro et al, 1996).

C57BL/10

Good reproductive performance (3/25) with colony output 1.4 young/female/week, litter size 6.9 (2/25) at weaning (Festing, 1976a). Intermediate breeding performance (12/24) (Hansen et al., 1973., 1973).


Miscellaneous

C57BL/Ka

High degree of genetic distinctiveness (3/27) (Taylor, 1972). \par

C57BL/6

High degree of genetic distinctiveness (4/27) (Taylor, 1972). Recommended host for the following transplantable tumours: mammary adenocarcinoma BW 10232 melanoma B16, myeloid leukaemia C 1498 and preputial gland carcinoma ESR586 (Kaliss, 1972).

Embryonic stem cell lines have been established (Kawase et al, 1994).

High rate of spontaneous mutations at the agouti and W loci (1/21) (Schlager and Dickie, 1967). \par

C57BL/10

High incidence of spontaneous `deviants' (possible mutants) (2/21) (Schlager and Dickie, 1967).

C57BLKS.

Origin: C57BL/6J to Biesele in 1947, then pen bred, to Kaliss in 1948. Ks resumed inbreeding. To J 1948. Differs from C57BL/6 and C57BL/10 at the Bgls, Bglt, cdm and H2 loci as a result of a genetic contamination, probably with a DBA substrain at the time the colony was pen-bred. Resembles B6 at the Lv locus (at which B6 and B10 differ). Formerly known as C57BL/Ks but renamed in Dec. 1994. Maint. by J.

Characteristics:

Low hepatic delta-aminolaevulinate dehydratase activity in Ks substrain (7/8) (Doyle and Schimke, 1969). High susceptibility to BALB/Tennant leukaemia virus in Ks substrain (3/12) (Tennant, 1965). Resistant to Herpes simplex virus (2/11) in Ks substrain (Lopez, 1975). High retinal ganglion cell number (22/24) (Williams et al, 1996).


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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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