Sci. Aging Knowl. Environ., 25 June 2003
Vol. 2003, Issue 25, p. as1

EXPERIMENTAL RODENT STRAINS

B6C3F1 Mouse

James M. Harper

The author is in the Department of Pathology & Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109, USA. E-mail: jmharper{at}med.umich.edu

http://sageke.sciencemag.org/cgi/content/full/sageke;2003/25/as1

Key Words: B6C3F1 hybrid mouse • caloric restriction • inbred mouse strain • mortality • pathologies of aging

Abstract: This document contains a summary of the biological characteristics of the B6C3F1 mouse, which is a first-generation hybrid strain produced by crossing C57BL/6 females and C3H males.


Strain B6C3F1. This is a first-generation (F1) hybrid strain produced by crossing C57BL/6 females and C3H males.
Species and taxonomy House mouse, Mus musculus. Order Rodentia; family Muridae (Old World rats and mice)
Source This strain is widely available from a number of commercial sources, including the National Institute on Aging (NIA). Until recently, NIA also supplied aged individuals, but these are currently unavailable as a result of genetic contamination in the breeding colony of one of the parent strains, C57BL/6, at commercial supplier Harlan Sprague Dawley (see "Spoiled Stores"). NIA predicts that aged B6C3F1 mice will become available again sometime in 2004. For more information, go to http://www.nia.nih.gov/research/policy.htm or contact Dr. Nancy Nadon at NadonN{at}nia.nih.gov.
Phenotype Coat color is agouti.
History and genetic background Parental C57BL/6 mice were derived from original stock acquired in 1921. The other parental strain, C3H, was developed by Strong in 1920 from a cross between a Bagg albino mouse and a dilute brown agouti (DBA) mouse. For additional information on strain history, see Festing 1998.

General comments. B6C3F1 is among the most widely used of all inbred mouse strains and has numerous substrains (Festing 1998). This general-purpose hybrid has been used in multiple research applications, particularly in toxicology and as embryo donors in transgenic research. Mice of this strain are smaller, on average, than those of the B6 parental strain. In the NIA/Biomarkers of Aging Program (BAP) study, body weights of B6C3F1 mice averaged about 40 g (for both sexes combined), which is about 4 g lighter than B6 mice (Turturro et al. 1999). Females averaged about 85% the size of males. Both sexes had reached peak body weight by around 20 months of age.

The B6C3F1 genome includes a Y chromosome of Asian M. musculus origin and a LINE-1 transposable element derived from the European mouse species M. spretus. The frequency of the LINE-1 element in mice from the B6 parental stock suggests that up to 6.5% of the genome may be of M. spretus origin. The pseudoautosomal regions of the X and Y chromosomes have a characteristic Pst I pattern of restriction fragment sizes that is present only in the C57BL family of inbred mouse strains.

Caveats for researchers in the field of aging. Inbred rodent strains vary a great deal in their longevities, aging patterns, and responses to caloric restriction. The median life span for ad lib-fed B6C3F1 hybrids (males and females combined) in the BAP study was 933 days, or about 11% longer than for ad lib-fed C57BL6, one of the parental strains. Reproductive life spans are correspondingly longer in hybrids than in C57 mice, but no other differences in reproductive output have been systematically noted. Substantial differences have also been demonstrated between strains with respect to aging-related pathologies (Lipman et al. 1999).

Mice of this strain exhibit a high incidence and severity of nerve lesions (Tabata et al. 2000a) associated with spontaneous age-related hypoglycemia (Tabata et al. 2000b). Their antioxidant defense systems may be up-regulated with age (Barnes et al. 1998). An age-related increase in the number of ovarian masses and cysts containing purulent material due to Klebsiella spp. infection has also been reported, but with a marked difference in the incidence of this lesion in B6C3F1 mice from different suppliers (Rao et al. 1987).

RESULTS OF MAJOR AGING STUDIES USING B6C3F1 MICE

The following results are from the life span study by BAP, NIA, Bethesda, MD, and the National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration, Jefferson, AR (Lipman et al. 1999 and Turturro et al. 1999). Longevity statistics were calculated from data provided by the NCTR.

Methodology (key aspects). This study involved lifelong (up to 37 months) comparison of ad lib-fed (AL) controls with 30% calorie-restricted (CR) mice, all housed in a specific pathogen-free barrier facility. Data included here are for mice fed NIH pelleted feed. Calorie restriction was initiated stepwise at 6 to 14 weeks of age and was increased over several weeks to 30% (for experimental details, see Turturro et al. 1999).

Statistical sample sizes. Longevity statistics were calculated for 56 AL females (AL-F), 56 CR females (CR-F), 56 AL males (AL-M), and 56 CR males (CR-M).

Maximum life span in days.

AL-F, 1224 (40.8 months); CR-F, 1489 (49.63 months)

AL-M, 1293 (43.1 months); CR-M, 1568 (52.27 months)

Mean life span (with coefficient of variation) in days.

AL-F, 905.93 (30.20 months) ± 12.96; CR-F, 1215.86 (40.53 months) ± 12.90

AL-M, 958.55 (31.95 months) ± 16.10; CR-M, 1257.27 (41.91 months) ± 15.06

Median life span (days).

AL-F, 922.50; CR-F, 1265.00; AL-M, 979.50; CR-M, 1337.50

Time until 80% mortality (days).

AL-F, 800; CR-F, 1066; AL-M, 827; CR-M, 1024

Pathology study parameters. Pathology data are from the BAP caloric restriction study described above, but from individuals other than those used to generate life span data (see Lipman et al. 1999 for the published report on pathology). B6C3F1 hybrid mice were killed at ages 6, 12, 18, 24, 30, and 36 months of age when sample sizes allowed this for the oldest groups. [Experimental groups had 14 to 15 animals at 6 months old and 29 to 32 animals in all remaining age-by-sex-by-AL/CR treatment group (that is, the total number of animals still alive at the later ages for all four groups combined).] All mice were shipped live by NCTR to the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, where they were killed and necropsied. Organs were fixed and histopathological analysis was performed. (The numbers of animals necropsied in each experimental group are shown below.) The average number of lesions per rat was analyzed by strain, sex, and diet group. Lesion prevalence in each strain was analyzed for 6-, 12-, 18-, 24-, 30-, and 36-month-old mice. (See Lipman et al. 1999 for more details on pathology methods and analysis.)

Most frequent lesions for strain (total n = 673; both sexes and all diet groups combined). In descending order of frequency (the number of cases is in parentheses), the five most frequent lesions were as follows: lymphoid nodules in the omentum (the portion of the peritoneum that covers the intestines) (291), salivary gland (247), kidney (243), bladder (223), and palate (181). The next most frequent were fibrous bone dystrophy (148), lymphoid nodule of Harderian gland (147), endometrial (ovarian) cysts (130), lymphoid nodule of lung (111), and tubular muscle aggregates (100).

Most common proliferative and degenerative lesions in older age groups (by sex and diet group, expressed as percentages; same abbreviations for experimental groups as used above. Percentages are shown in parentheses).

AL-F (30 and 36 months combined) (n = 35): Lymphoid nodule of salivary gland (77); thyroid cysts (74); fibrous bone dystrophy (71); endometrial cysts (63); lymphoid nodules of kidney (66), omentum (66) or liver (54); abnormal ovarian pigmentation (51); lymphoid nodule of lung (46).

AL-M (30 and 36 months combined) (n = 59): Tubular muscle aggregates (85), lymphoid nodules of salivary gland (69) or palate (56), tooth socket inflammation (54), dilated kidney tubules (46).

Summary. Although no inferential statistical results are available, caloric restriction appears to have substantially reduced the prevalence of most of the pathological lesions reported in this study.


June 25, 2003
  1. C. J. Barnes, W. E. Hardman, G. L. Maze, M. Lee, I. L. Cameron, Age-dependent sensitization to oxidative stress by dietary fatty acids. Aging (Milano) 10, 455-462 (1998).
  2. M. F. W. Festing, Inbred strains of rats and their characteristics. Mouse Genome Informatics, The Jackson Laboratory (1998) (http://informatics.jax.org/external/festing/mouse/INTRO.shtml).
  3. R. D. Lipman, G. E. Dallal, R. T. Bronson, Lesion biomarkers of aging in B6C3F1 hybrid mice. J. Gerontol. A Biol. Sci. Med. Sci. 54, B466-B477 (1999). [Medline]
  4. G. N. Rao, R. L. Hickman, S. K. Seilkop, G. A. Boorman, Utero-ovarian infection in aged B6C3F1 mice. Lab Anim. Sci. 37, 153-158 (1987).[Medline]
  5. R. L. Sprott, S. N. Austad, in Handbook of the Biology of Aging, E. L. Schneider, J. W. Rowe, Eds. (Academic Press, New York, ed. 4, 1995).
  6. H. Tabata, H. Ikegami, K. Kariya, A parallel comparison of age-related peripheral nerve changes in three different strains of mice. Exp. Anim. 49, 295-299 (2000).[CrossRef][Medline]
  7. H. Tabata, H. Ikegami, K. Kariya, Spontaneous age-related peripheral neuropathy in B6C3F1 mice. J Toxicol Sci 25, 95-104 (2000).
  8. A. Turturro, W. W. Witt, S. Lewis, B. S. Hass, R. D. Lipman, R. W. Hart, Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. J. Gerontol. A Biol. Sci. Med. Sci. 54, B492-B501 (1999).[Abstract/Free Full Text]
  9. Unpublished Data on Spontaneous Neoplastic Lesions in B6C3F1 mice, Charles River Laboratories Technical Document (http://www.criver.com/techdocs/89feb_sn).
  10. Unpublished Survival Data on Longevity Groups, National Institute on Aging/National Center for Toxicology Research: http://sageke.sciencemag.org/cgi/content/full/sageke;2003/25/as1/DC1
Citation: J. M. Harper, B6C3F1 Mouse. Sci. SAGE KE 2003, as1 (25 June 2003)
http://sageke.sciencemag.org/cgi/content/full/sageke;2003/25/as1








Science of Aging Knowledge Environment. ISSN 1539-6150