Sci. Aging Knowl. Environ., 5 November 2003
Vol. 2003, Issue 44, p. as3
[DOI: 10.1126/sageke.2003.44.as3]

EXPERIMENTAL RODENT STRAINS

DBA/2 Mouse

Donna J. Holmes

The author is in the Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA. E-mail: electric{at}uidaho.edu

http://sageke.sciencemag.org/cgi/content/full/sageke;2003/44/as3

Key Words: DBA/2 mouse • caloric restriction • inbred mouse strain • mortality • pathologies of aging

Abstract: This document contains a summary of the biological characteristics of the DBA/2 mouse. This strain is available from the National Institute on Aging.


Strain DBA/2 mouse; inbred laboratory mouse strain; abbreviated as D2.
Species and taxonomy House mouse, Mus musculus. Order Rodentia; family Muridae (Old World rats and mice).
Source DBA/2 mice are widely available from a number of commercial sources, including the National Institute on Aging (NIA) and National Institutes of Health (NIH). Until recently, NIH also supplied aged individuals, but these are currently available only in limited quantities as a result of genetic contamination in the breeding colony of one of the parent strains at commercial supplier Harlan Sprague-Dawley (see "Spoiled Stores"). No calorie-restricted animals are available at this time. 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 These mice have a light-brown or "dilute" brown coat. They are smaller than C57BL/6 mice: weight about 30 g.
History and genetic background Parental strain DBA is the oldest of inbred mouse strains and dates back to Little 1909. The DBA/2 substrain was started around 1930. Festing (1998) notes that the substantial differences between DBA substrains are probably too large to be attributable to mutation alone and are more likely a result of residual heterozygosity.

General comments. DBA/2 is a widely used inbred laboratory mouse strain, particularly in studies of cardiovascular biology, neurobiology, and neurosensory phenomena. Breeding performance is low relative to that of other strains. Of the mouse strains available from NIA, DBA/2 has the smallest body size.

Caveats for researchers in the field of aging. Inbred rodent strains vary considerably in terms of their longevities and aging patterns, as well as in the incidence and frequency of pathologies of aging. Longevity and incidence of tumors and other aging-related lesions vary substantially within individuals of each strain, as well as between strains, as may responses to aging-related experimental manipulations such as caloric restriction. Possible strain-specific effects of the timing and duration of caloric restriction on longevity and pathology incidence are also important considerations for researchers selecting inbred rodent strains for aging studies. DBA/2 mice have been reported both to respond to caloric restriction differently and to exhibit shorter life spans than other inbred mouse strains (Turturro et al., 1999; Forster et al., 2003; see summary below); these effects should be considered when using this strain in studies of aging. Estrous cycles in females are shorter and less regular than those in other laboratory mouse strains (Nelson et al., 1992), hence patterns of reproductive aging in DBA/2 females may differ as well.

A low susceptibility to atherosclerotic aortic lesions in response to an atherogenic diet has been noted for this strain. DBA/2 mice are homozygous for a mutation for aging-related hearing loss (ah1), resulting in detectable high-frequency impairment (and progressive cochlear pathology) by the time of weaning and severe impairment by 2 to 3 months of age. Young individuals are prone to audiogenic seizures. Adults develop progressive visual abnormalities, including iris aberrations, resembling hereditary glaucoma in humans; these are generally seen in both sexes by 9 months of age. This strain is particularly intolerant of alcohol and morphine. In addition, these mice may not be suitable for studies of normal aging-related changes in behavior or cognition, because they have a low brain weight on average and perform poorly in general on a number of standard psychological tests, including forced swimming tests.

RESULTS OF MAJOR AGING STUDIES USING DBA/2 MICE

Major study. Life span study, Biomarkers of Aging Program (BAP), NIA, Bethesda, MD, and National Center for Toxicological Research (NCTR), Food and Drug Administration, Jefferson, AR (see Lipman et al., 1999; Turturro et al., 1999). Longevity statistics were calculated from data provided by NCTR (Angelo Turturro, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR).

Methodology (key aspects). The BAP study involved lifetime (up to 37 months) comparison of ad lib-fed (AL) controls with 40% calorie-restricted (CR) mice, all housed in a specific pathogen-free (SPF) barrier facility and fed NIH or Pur pelleted feed. Three other mouse strains were included: C57BL/6NNia and B6D2F1 and B6C3F1 hybrids. All were maintained in an SPF barrier facility. Mice were fed NIH-31 open-formula pelleted diet; CRs were fed a calorie-reduced vitamin-supplemented version of NIH-31. CR was initiated stepwise at 6 to 14 weeks of age and was increased over several weeks to 40%. For experimental details, see Turturro et al., 1999.

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

Maximum life span (MLS) in days. AL-F, 1015 (33.83 months); CR-F, 1060 (35.33 months); AL-M, 934 (31.13 months); CR-M, 1069 (35.63 months).

Mean life span (with coefficient of variation) in days. AL-F, 512.64 (17.09 months) ± 51.59; CR-F, 702.82 (23.42 months) ± 40.07; AL-M, 544.88 (18.16 months) ± 47.61; CR-M, 716.64 (23.89 months) ± 28.79.

Median life span (days). AL-F, 540; CR-F, 827; AL-M, 616; CR-M, 727.

Time until 80% mortality (days). AL-F, 737; CR-F, 943; AL-M, 789; CR-M, 909.

Summary. In the BAP study, ad lib-fed D2 mice were markedly shorter lived (median life span, 540 and 616 days for females and males, respectively) than C57BL/6s (median 816 and 843 days for females and males, respectively) or B6C3F1 or B6D2F1 hybrids. The differential between the sexes in the effects of caloric restriction in the BAP study was greater than for other mouse strains.

Pathology data are unavailable for DBA/2 mice from the BAP study. An earlier, comparable, long-term study, however, documents a reliable effect of 40% caloric restriction in delaying the onset of aging-related pathologies in this mouse strain, as well as others later included in the BAP project (Bronson and Lipman, 1991). More recently, Forster et al. (2003) report that caloric restriction failed to increase either median or maximum life span in D2 mice and actually increased mortality risk when initiated at older ages (17 to 24 months). In this later study, D2 mice also exhibited considerably shorter life spans than reported for this same strain in the BAP study.


November 5, 2003
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Citation: D. J. Holmes, DBA/2 Mouse. Sci. Aging Knowl. Environ. 2003 (44), as3 (2003).








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