Sci. Aging Knowl. Environ., 17 November 2004
Vol. 2004, Issue 46, p. as4
[DOI: 10.1126/sageke.2004.46.as4]

EXPERIMENTAL RODENT STRAINS

F344BNF1 and BNF344F1 Hybrid Rats

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/2004/46/as4

Key Words: Brown Norway rat • Fischer 344 rat • F344BNF1 hybrid rat • BNF344F1 hybrid rat • hybrid rat strain

Abstract: This document contains a summary of the biological characteristics of the F344BNF1 and BNF344F1 hybrid rats, which are the result of crosses between Brown Norway and Fischer 344 rats. The F344BNF1 hybrid is available from the National Institute of Aging.


Strain Hybrid laboratory rat strains. The F344BNF1 hybrid rat is also abbreviated as F344xBNF1 or F3BNF1 [for a Fischer 344 (F344) x Brown Norway (BN) F1 hybrid cross with Fischer (F344/Nia) mothers], and the BNF344F1 hybrid rat is also abbreviated as BNF3F1 [for a BN x F344 F1 hybrid cross with BN (BN/Rij) mothers].
Species and taxonomy Norway rat, Rattus norvegicus. Order Rodentia; family Muridae (Old World rats and mice).
Source F344BNF1 rats are available from the National Institute on Aging (NIA) of the National Institutes of Health (NIH). For more information go to http://www.nia.nih.gov/ResearchInformation/ScientificResources/ or contact Dr. Nancy Nadon at NadonN{at}nia.nih.gov.
Phenotype This strain has a brown coat with a white stripe or patch on the underbelly.
History and genetic background See SAGE KE information on the parental strains:
Brown Norway Rat
Fischer 344 (F344) Rat
Descriptions of the parental strains have been prepared by Festing (1998):
Brown Norway Rat
F344 Rat
NIH began offering hybrids in the early 1990s and continues to supply F344BNF1 rats.

General comments. Hybrid rats are bigger than those of either parental strain. In the NIH/Biomarkers of Aging Program (BAP) study, F3BNF1 rats averaged about 493 g (sexes combined), which is 9 to 12% larger than Fischer 344 rats and about 25 percent larger than BN rats (Tuturro et al. 1999). Females averaged about twice the weight of males. Both sexes reached peak body size at around 28 months, significantly later than either parental strain.

F3BNF1 and BNF3F1 rats should not be considered to be either genetically or phenotypically identical, because of the possibility of maternal effects, including genomic imprinting. Investigators should refer to summaries of each of the parental strains for information on their respective genetic background and origins.

Caveats for researchers in the field of aging. Inbred rodent strains vary greatly in terms of their longevities and aging patterns, and the differences between these two F1 hybrid rats and their parental strains are particularly striking. Both F1s are significantly longer-lived than either parental strain, with correspondingly longer reproductive life spans. (No other differences in reproductive output have been systematically noted.) There are also significant differences in aging-related pathologies between hybrid and parental strains, including frequencies, overall incidence, and number of lesions per individual (Bronson 1990; Lipman et al. 1996; Lipman et al. 1999). With only a couple of exceptions, both hybrid strains have been shown to have fewer lesions per animal and a lower lesion incidence overall than either BNs or F344s. This means that hybrids offer researchers a longer life span in which to study healthy aging processes in the absence of definable aging-related pathology (Lipman et al. 1996). Because the overall differences in aging are relatively small, however, NIH has elected to offer only the F3BNF1 hybrid (N. Nadon, personal communication).

RESULTS OF MAJOR AGING-RELATED STUDIES USING F344BNF1 and BNF344F1 HYBRID RATS

The following results are from the life-span study of BAP, NIA, Bethesda, MD, and the National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration, Jefferson, AR, which included F3BNF1 hybrids only. Longevity statistics were calculated from data provided by NCTR. (See Turturro et al. 1999 for longevity data and Lipman et al. 1999 for data on incidence and frequency of aging-related pathological lesions).

Methodology (key aspects). BAP study: Lifetime (up to 37 months) comparison of ad lib (AL)-fed controls with 40% calorie-restricted (CR) rats. Three rat strains (F344/Nia, BN/Rij, and F3BNF1 hybrids) and four mouse strains [C57BI/6NNia; D2 (DBA/2JNia); B6D2F1; and C3H (B6C3F1) (hybrids)] were included in this study. All were maintained in a specific pathogen-free (SPF) barrier facility. All hybrid rats were fed the NIH diet; CRs were fed a calorie-reduced vitamin-supplemented version of this same diet. CR was initiated stepwise at 6 to 14 weeks of age and increased over several weeks to 40%. (For more experimental details, see Turturro et al. 1999.)

Statistical sample sizes (for entire life-span study, F3BNF1s only). Longevity statistics calculated for 48 ad lib-fed females (AL-F), 44 calorie-restricted females (CR-F), 46 ad lib-fed males (AL-M), and 45 calorie-restricted males (CR-M).

Maximum life span (MLS) in days. AL-F, 1194 (39.8 months); CR-F, 1622 (54.07 months); AL-M, 1257 (41.9 months); CR-M, 1661 (52.03 months)

Mean life span (with coefficient of variation) in days. AL-F, 969.33 (32.31 months) ± 14.22; CR-F, 1298.2 (43.27 months) ± 15.61; AL-M: 931.24 (31.04 months) ± 26.53; CR-M, 1218.93 (40.63 mos) ± 14.20.

Median life span (days). AL-F, 957; CR-F, 983; AL-M, 1018; CR-M, 1226.

Time until 80% mortality (days). AL-F, 1094; CR-F, 1530; AL-M, 1132; CR-M, 1356.

Pathology study parameters. Data are from the BAP caloric restriction study as described for F3BNF1 hybrid rats (Lipman et al. 1999). [Although the hybrid strain was designated BNF3F1 in Lipman et al. 1999, mothers were actually BN rats (C. Schmeider, NCTR, and R. Lipman, personal communication), hence standard nomenclature dictates that they be referred to as F3BNF1.]

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 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 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 (total n = 631 rats; both sexes and all diet groups combined). Lesions are given in descending order of frequency, and the number of cases is shown in parentheses.

Lymphoid nodule in lung* (398)

Focal mineralization, kidney* (254)

Spinal root degeneration (210)

Tracheal gland cyst (112)

Urothelial hyperplasia (kidney)* (103)

Pituitary adenoma* (92)

Fibrosis, heart* (90)

Cystic glands in stomach (80)

Lymphoid nodule in kidney* (69)

Focus of enlarged, pale adrenal cells* (67)

[*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 = 73): Mineralization, kidney (94.5); lymphoid nodule, lung (65.8); pituitary adenoma (53.4); urothelial hyperplasia, renal pelvis of kidney (37.0); spinal root degeneration (32.9).

AL-M (24 and 30 months combined) (n = 85): Lymphoid nodule, lung (44.7); spinal root degeneration (42.4); enlarged pale cells, adrenal (32.9); fibrosis in heart (31.8); lymphoid nodule in kidney (29.4).

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 ≤ 0.01 are included. Symbols and abbreviations are as follows: P indicates level of statistical significance; {beta} is equal to the y intercept of the regression line; positive {beta} indicates greater prevalence in CR animals; negative {beta} indicates greater prevalence in AL animals; and 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: Foci of pale-staining cells. Diet: P = 0.001, {beta} = –1.45, OR = 0.24

Kidney: Lymphoid nodule. Diet: P = 0.001, {beta} = –1.29, OR = 0.28

Kidney: Protein casts. Diet: P = 0.001, {beta} = –1.34, OR = 0.84

Liver: Bile duct hyperplasia. Diet: P = 0.001, {beta} = –1.67, OR = 0.19

Lung, Lymphoid nodule. Diet: P = 0.006, {beta} = –1.40, OR = 0.25. Diet x age: P = 0.006, {beta} = 0.05, OR = 1.06

Pancreas: Islet cell hyperplasia. Diet: P = 0.006, {beta} = –2.08, OR = 0.12

Pituitary adenoma. Diet: P = 0.001, {beta} = –1.64, OR = 0.19

Renal pelvis, kidney: Urothelial hyperplasia. Diet: P = 0.001, {beta} = –4.23, OR = 0.02. Diet x age: P = 0.001, {beta} = 0.12, OR = 1.12

Spinal root degeneration. Diet: P = 0.001, {beta} = –5.35, OR = 0.01. Diet x age: P = 0.001, {beta} = 0.18, OR = 1.20

Summary. In the NIA/BAP study overall, caloric restriction increased average life span of females by about 20%, and that of males by about 14%. For all rat strains in this study, including hybrids, 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 the 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). Results of this study confirmed those earlier studies on F3BNF1 hybrids suggesting that as well as being longer-lived, hybrids display a later onset and lower overall occurrence of most common pathological lesions. Both interstrain and intersex differences, however, depend to an unknown extent on chance variation among individuals and differed markedly in this study from those found in previous work (compare, for example, Bronson 1990, Lipman et al. 1996, and Lipman et al. 1999).

In the NIA/BAP study, four lesions were distributed similarly among both sexes in F3BNF1 rats: kidney protein casts, lymphoid nodules in the liver, stomach cysts, and tracheal cysts. The effect of sex on the prevalence of the most common lesions differed substantially among the three rat strains in this study. The incidence of the following nine common aging-related pathologies was significantly higher in BN females than in female F344s or F3BNF1 hybrids: cortical hyperplasia, cytoplasmic vacuolization, and enlarged pale cells in adrenal gland; hydronephrosis, mineralization, and protein casts in kidney; pancreatic atrophy; pituitary adenoma. The following eight had a significantly higher incidence in F344 than in either BN or F3BNF1 hybrid females: enlarged pale cells in adrenal gland; Harderian gland metaplasis of exorbital gland; heart fibrosis; glomerulonephropathy, protein casts, and mineralization in kidney; bile duct hyperplasia; leukemia; retinal degeneration; and C-cell hyperplasia. Three lesions occurring significantly more often in F3BNF1 females than in females of either parental strain were kidney mineralization, pituitary adenoma, and thyroid cysts.

Ten lesions occurred significantly more often in BN males than in either F344 or F3BNF1 males: foci of cytoplasmic vacuolization, foci of enlarged pale adrenal cells, Harderian gland metaplasia, hydronephrosis, lymphoid nodules in lung, islet cell hyperplasia or atrophy of pancreas, urothelial hyperplasia; testicular atrophy, and thyroid cysts. F344 males had the following six lesions at higher prevalence than either BN or F3BNF1 males: glomerulonephropath, bile duct hyperplasia, leukemia, retinal degeneration, Leydig cell adenoma, and thyroid C-cell hyperplasia. The only lesion with a significantly higher incidence in F3BNF1 hybrid males than in either parental strain was lymphoid nodule in kidney.


November 17, 2004

Suggested ReadingBack to Top

  • R. T. Bronson, in Genetic Effects of Aging II, D. E. Harrison, Ed. (Telford Press, Caldwell, NJ, 1990), pp. 279-358.
  • M. F. W. Festing, Inbred strains of rats and their characteristics. Mouse Genome Informatics, The Jackson Laboratory (1998) (http://www.informatics.jax.org/external/festing/rat/docs/BN.shtml and http://www.informatics.jax.org/external/festing/rat/docs/F344.shtml).
  • R. D. Lipman, C. E. Chrisp, D. G. Hazzard, R. T. Bronson, Pathologic characterization of Brown Norway, Brown Norway x Fischer 344, and Fischer 344 x Brown Norway rats with relation to age. J. Gerontol. A Biol. Sci. Med. Sci. 51, B54-B59 (1996). [Abstract]
  • R. D. Lipman, G. E. Dallal, R. T. Bronson, Effects of genotype and diet on age-related lesions in ad libitum fed and calorie-restricted F344, BN, and BNF3F1 rats. J. Gerontol. A Biol. Sci. Med. Sci. 54, B478-B491 (1999). [Abstract]
  • 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]
  • Unpublished Survival Data on Longevity Groups, NIA/National Center for Toxicology Research (http://sageke.sciencemag.org/cgi/content/full/2004/46/as4/DC1).
Citation: D. J. Holmes, F344BNF1 and BNF344F1 Hybrid Rats. Sci. Aging Knowl. Environ. 2004 (46), as4 (2004).








Science of Aging Knowledge Environment. ISSN 1539-6150