Sci. Aging Knowl. Environ., 22 September 2004
EXPERIMENTAL RODENT STRAINS
Brown Norway Rat
Donna J. Holmes
The author is in the Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA. E-mail: email@example.com://sageke.sciencemag.org/cgi/content/full/2004/38/as3
Key Words: Brown Norway rat BN rat inbred mouse strain autoimmune disease
Abstract: This document contains a summary of the biological characteristics of the Brown Norway rat. This strain is available from the National Institute of Aging.
General comments. Festing (1998) noted that BN rats are "somewhat vicious" and have lower fertility than other inbred rat strains. In the NIH/Biomarkers of Aging Program (BAP) study, body weights of BN rats averaged 367.5 g (based on peak adult weights for males and females combined), which is about 83% of the average weights of F344 rats and about 75% of the average weights of BNF3F1 hybrids (study details are shown below). Males averaged about twice the weight of females.
Caveats for researchers in the field of aging. Lipman et al. (1999) noted that differences in aging-related pathologies, or the "aging phenotype," in BN rats relative to other strains, including F344, may be attributable to their derivation from a different ancestral strain. BN rats have been noted to display poor performance in an active avoidance learning task but to have good reference memory. Behavioral performance has been noted to decline more slowly with age in BN rats than in F344 rats. BN rats respond more quickly than F344 rats to the induction of hypertension using deoxycorticosterone acetate salt. This strain has been used extensively in immunological studies, especially those involving the experimental induction of autoimmune diseases. They do not develop graft/host disease, and they show a low antibody response to phytohemagglutinin, concanavalin A, and strep group A carbohydrate. Susceptibilities to other aging-related and experimentally induced diseases are outlined in Festing (1998) and Lipman et al. (1999).
RESULTS OF MAJOR AGING STUDIES USING BN RATS
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, Tuturro et al. 1999). Longevity statistics were calculated from data provided by NCTR.
Methodology (key aspects). BAP study: Lifetime (up to 37 months) comparison of ad lib-fed (AL) controls with 40% calorie-restricted (CR) rats. Three rat strains (F344, BN, and BNF3F1 hybrids) and four mouse strains [C57BI/6NNia; D2 (DBA/2JNia); B6D2F1; and C3H (B6C3F1) hybrids] were included in the study. All were maintained in a specific pathogen-free (SPF) barrier facility. All BN rats were fed the NIH diet; CR rats were fed a calorie-reduced vitamin-supplemented version of this same diet. Caloric restriction was initiated stepwise at 6 to 14 weeks of age and increased over several weeks to 40%. (For more experimental details, see Tuturro et al. 1999.)
Statistical sample sizes (for entire life span study; BN rats only). Longevity statistics were calculated for 47 AL females (AL-F), 48 CR females (CR-F), 47 AL males (AL-M), and 48 CR males (CR-M).
Maximum life span in days. AL-F, 1195 (39.83 months); CR-F, 1429 (47.63 months); AL-M, 1120 ( 37.33 months); CR-M, 1362 (45.40 months).
Mean life span (with coefficient of variation) in days. AL-F, 908.83 (30.29 months) ± 16.73; CR-F, 1123.77 (37.46 months) ± 20.06; AL-M, 863.02 (28.77 months) ± 22.89; CR-M, 993.98 (33.13 months) ± 34.24.
Median life span (days). AL-F, 930; CR-F, 1162; AL-M, 903; CR-M, 1050.
Time until 80% mortality (days). AL-F, 1026; CR-F, 1288; AL-M, 1052; CR-M, 1245.
Pathology study parameters. Data are from the BAP caloric restriction study as described above, but from individual rats other than those used to generate life span data (see Lipman et al. 1999 for the published report on pathology; this report includes F344, BN, and BNF3F1 hybrid rats only). Rats were killed at ages 12, 18, 24, 30, and 36 months, when sample sizes in the oldest groups allowed. The initial experimental groups had 30 animals in each (age x sex x diet) treatment group, and animals were shipped live by NCTR to Jean Mayer, U.S. Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA, where they were killed, fixed, and necropsied, and histopathological analysis was performed. (The number of animals necropsied in each experimental group is 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 24- and 30-month-old groups only. Only the most prevalent or reliably age-associated lesions are included here, especially those likely to be proliferative or degenerative with age.
Most frequent lesions for BN rat strain (total n = 572 rats; both sexes and all diet groups combined). Lesions are given in descending order of frequency, and the number of cases in shown in parentheses.
Lymphoid nodule in lung* (304)
Hydronephrosis (kidney)* (257)
Ganglioneuroma of adrenal gland* (202)
Testicular atrophy (males)* (166)
Spinal root degeneration* (142)
Alveolar histiocytosis (lung) (134)
Focal cytoplasmic vacuolization of adrenal gland (88)
Exocrine atrophy of pancreas (77)
Islet cell hyperplasia (pancreas)* (62)
Urothelial hyperplasia of renal pelvis (62)
[*Indicates lesions that were also among the five most prevalent types (listed below) in either sex at 24 and 30 months.]
Most common proliferative and degenerative lesions in older age groups (by sex and diet group, expressed as percentages). Abbreviations for experimental groups are the same as used above. Percentages are shown in parentheses.
AL-F (24 and 30 months combined) (n = 43): Lymphoid nodule in lung (81.4); spinal root degeneration (76.7); fibrosis of uterus (72.1); enlarged pale cells in adrenal gland (72.1); hydronephrosis (kidney) (69.8).
AL-M (24 and 30 months combined) (n = 85): Testicular atrophy (81.2); enlarged pale cells in adrenal gland (72.9); lymphoid nodule in lung (63.5); hydronephrosis (kidney) (61.2); hyperplasia of pancreatic islet cells (45.9); spinal root degeneration (45.9).
Lesions with frequencies reliably reduced by caloric restriction in rats 30 months (that is, significantly associated either with diet group or age x diet group interaction, as determined by log odds-ratio linear regression analysis). Only lesions with P 0.005 are included. Symbols and abbreviations are as follows: P indicates level of statistical significance; is equal to the y intercept of the regression line; positive indicates greater prevalence in CR animals; negative indicates greater prevalence in AL animals; OR equals odds ratio [this can be used to estimate odds that an animal in a specific experimental group will have a lesion of interest (see Lipman et al. 1999 for details)].
Adrenal: Focal cortical hyperplasia. CR: P = 0.001, = 0.96, OR = 0.38.
Adrenal: Focal cytoplasmic vacuolization. CR: P = 0.001, = 1.14, OR = 0.32.
Heart fibrosis. CR: P = 0.001, = 2.38, OR = 0.09.
Hydronephrosis (kidney)*. CR: P = 0.001; = 0.75; OR = 0.47.
Pancreatic atrophy. CR: P = 0.002, = 5.64, OR = 281.80; age x CR: P = 0.001, = 0.27, OR = 0.76.
Pancreatic islet cell hyperplasia. CR: P = 0.001, = 3.56, OR = 0.03.
Urothelial hyperplasia: Renal pelvis. CR: P = 0.002, = 2.99, OR = 0.05.
Spinal root degeneration. CR: P = 0.001, = 12.17, OR = 999.0; age x CR: P = 0.001, = 0.50, OR = 0.61.
Testicular atrophy. CR: P = 0.001, = 2.83, OR = 16.92; age x CR: P = 0.001, = 0.13, OR = 0.88.
Uterine fibrosis. CR: P = 0.001, = 2.81, OR = 0.06.
Summary. In the entire study overall, female control (AL) BN rats were about 10% longer lived, on average, than female F344 controls; male BN controls were 20% longer lived than male F344 controls. Caloric restriction increased the average life span of females by about 20% and that of males by about 14%. This effect was more pronounced in BN than in F344 rats.
For all three rat strains in this study combined, the most common pathological lesions increased in prevalence with age, and many were never seen in rats under 18 months. Caloric restriction significantly reduced the occurrence of most common lesions overall, and the total burden of age-associated pathology was reliably higher in AL than in CR diet groups at all ages from 12 to 30 months (only CR animals were included at 36 months). Nine commonly occurring lesions were more frequent in BN than in F344 or BNF3F1 hybrid females: cortical hyperplasia, cytoplasmic vacuolization or enlarged pale cells in the adrenal gland, heart degeneration, protein casts or hydronephrosis in the kidney, pancreatic atrophy, spinal root degeneration, and uterine fibrosis. For BN males, the more frequent lesions were focal cytoplasmic vacuolization or enlarged pale cells in adrenal glands, Harderian gland metaplasia, hydronephrosis (kidney), lymphoid nodules in the lung, pancreatic islet-cell hyperplasia, pancreatic atrophy, urothelial hyperplasia (kidney), testicular atrophy, and thyroid cysts. In other words, the aging phenotypes of BN rats of both sexes differed from those of F344 and BNF3F1rats in this study. Such differences, however, may depend a great deal on chance variation among individuals and have been shown to vary markedly from study to study (Lipman et al. 1996, 1999).
September 22, 2004
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Citation: D. J. Holmes, Brown Norway Rat. Sci. Aging Knowl. Environ. 2004 (38), as3 (2004).
Science of Aging Knowledge Environment. ISSN 1539-6150