Origin: Curtiss and Dunning 1920 at Columbia University Institute for Cancer Research,To Heston 1949 (Billingham and Silvers 1959). To National Institutes of Health in 1951 (Hansen et al 1982). Subsequent sublines from Dunning or NIH. This is easily the most widely used general-purpose inbred rat strain, being particularly favoured for cancer research and toxicology. There is now considerable background information on strain characteristics, including life-span, spontaneous diseases and response to chemicals.
Tumours: Mammary tumours 41% in females and 23% in males, pituitary adenomas 36% in females and 24% in males, testicular interstitial cell tumours 85% in males. Other tumour types less common (Sass et al 1975). Thyroid carcinoma 22% (Lindsey et al 1968). Interstitial cell testicular tumours 65%, mononuclear cell leukaemia 24%, subcutaneous fibroadenoma 9% in females. Both sexes have a 5% incidence of nodular hyperplasia of the liver. (Davey and Moloney 1970). In various studies incidence of leukaemias 23-26% and of testicular intersticial tumours 65-90% (Jacobs and Huseby 1967, Davey and Moloney 1970, Moloney et al 1970, Sass et al 1975, Cockrell and Garer 1976). Uterine polyploid tumours of endometrial origin 21% (Jacobs and Huseby 1967). In germ-free conditions leukaemia 26% in males, 36% in females, mammary tumours 12% in males 20% in females, all other tumours 9% in males, 5% in females (Sacksteder 1976).
Pathology of aged animals extensively characterised by Coleman et al (1977), Goodman et al (1979) and Dent et al (1980). Aged rats exhibit peripheral retinal degeneration which is exacerbated by fluorescent light of moderate intensity (32 foot-candles). They also develop cardiomyopathy with myocardial degeneration, fibrosis and chronic intersticial myocarditis (males 33%, females 18%) and nephropathy (67% in males, 39% in females) (Lai et al 1979). Retinas of both sexes show a steady decline with age in the thickness of the outer nuclear layer and photoreceptor layer, with a drastically accelerated rate of peripheral retinal degeneration seen only in males after 12 months of age (Diloreto et al, 1994, see also Faktorovich et al, 1992).
Neurological toxicity of polybrominated biphynals and acrylamide described by Tilson et al (1978) and Tilson and Cabe (1979a,b). Low biliary excretion of copper after intravenous injection of CuSO4 (4/4) (Nederbragt and Lagerwerf 1986). Susceptible to the induction of tumours of the tongue by 4-nitroquinoline-1-oxide (Tanaka et al 1993). Susceptible to the development of anaplastic astrocytomas and glioblastomas following treatment with N-methyl-N-nitrosourea in the drinking water (Shibutani et al 1993). Isolated tracheal rings hyperresponsive to carbachol compared with LEW and F344 (Jia et al 1995). Realtively insensitive to the induction of tumours by N-methyl-N-nitrosourea (MNU) following treatment with cyproterone acetate which caused a high incidence of tumours in the outbred Cpb:WU strain (Bosland et al, 1992a). However, treatment with cyproproterone acetate for 21 days, testosterone proprionate for three days and a single i.p. injection of MNU results in atypical hyperplasia of the ventral prostate (Bosland et al, 1992b).
Severity of spontaneous nephropathy in aged rats reduced by treatment with arylsulfonylurea (Milman et al 1979). Exposure of weanling rats to terephthalic acid or dimethyl terephthalate in the diet induced urolithiasis (Wolkowski et al 1982). Phenylketonurea can be induced by p-Chloro-DL-phenylalanine with L-phenylalanine (Andersen and Guroff 1974, Anderson 1982). Bleomycin induces pulmonary fibrosis, which can be reduced by treatment with indomethacin (Thrall et al 1979) . Treatment with 3,2'-dimethyl-4-aminobiphenyl (DMAB) provides the best model for prostatic cancer of five tested (Shirai et al 1990). Slow metaboliser of MPPB (LEW is fast) (Takahara et al 1993). Morphene does not increase nose-poking behaviour, and phenobarbital does not decreases it, in contrast with strain NBR (Witkin and Goldberg, 1992). Compared with LEW rats, F344 show a much lower preference for several classes of drugs of abuse. This may be associated with levels of neurofilament proteins in the ventral tegmental area of the brain (Guitart et al, 1992). Duration of morphine-induced EEG slow-wave bursts and associated behavioural stupor was less in F344 than in LEW (Myomichelson and Young, 1993). F344 rats self-administer less morphine than LEW rats (Gosnell and Krahn, 1993). Duration of EEG slow-wave bursts and behavioural stupor also shorter in F344 than in LEW following administration of ethylketocyclazocine, suggesting differences in opioid-related receptor populations between these strains (Mayomichelson and Young, 1993). Resistant (1/4) to the organophosphate diisopropyl fluorophosphate (DFP) in terms of hypothermic response and recovery of day-night difference in core temperature (Gordon and Watkinson, 1995).
Resistant (compared with Sprague-Dawley rats) to the ventricular hypertrophy and pressure changes induced by monocrotaline. This is associated with pulmonary vascular response rather than hepatic metabolism (Pan et al, 1993).
Oral administration of hydroquinone for two years resulted in dose-related nephropathy and renal tubule adenomas in males but not females, whereas Sprague-Dawley rats were resistant (English et al, 1994). Sensitive to the convulsive effects of kainic acid (2/4) (Golden et al, 1995). Relatively resistant (1/3) to carcinogenic effects of tamoxifen, possibly associated with reduced cell proliferation in the liver (Carthew et al, 1995).
Low antibody response to streptococcal group A carbohydrate, not linked to the MHC (Stankus and Leslie 1976). Neonatal pancreatic islets derived by non-enzymic (in vitro) isolation procedures can be transplanted across MHC barriers without any immune suppression, in contrast with other strains such as ACI (Ketchum et al, 1992). Tachykinins cause bronchoconstriction in susceptible F344 mainly by an indirect mechanism that involves stimulation of NK1 receptors and mast cell activation, in contrast with the less sensitive strain BDE where they cause bronchoconstriction by a direct effect on the airway smooth muscle via activation of NK2 receptors (Joos et al, 1994).
Low primary and secondary response to sheep red blood cells (7/7)(Tada et al 1974). Poor producers of reaginic antibody in response to ovalbumin in aluminium hydroxide (Murphy et al 1974). Bouleter and Sell (1985) have described the alphafetoprotein and albumin genes and compared these with ACI andf BUF. Haematology; high RBC (7/7), Hb (6/7), PCV (6/7), and monocytes (6/7), but low MCV (1/7), MCH (1/7), MCHC (2/7) (Lovell et al 1981). See also Festing et al (1984).
Biochemistry and physiology
Growth described by Cameron et al (1985). Resistant to the development of salt-induced hypertension (Hall et al 1976). High specific activity but low inducibility of NADP cytochrome C reductase compared with outbred Sprague-Dawley rats (Gold and Widnell 1975). Hepatic microsomal activity before and after induction by phenobarbitone well characterised (Page and Vesell 1969, Gold and Widnell 1975, Dent et al 1980). Large pituitaries, susceptible to Cysticercus in infection and rapid absorption of diethylstilboestrol leading to death (Dunning et al 1947). Low LD50 of pentobarbital sodium (5/7=70mg/kg) (Shearer et al 1975). Have substantially higher levels of diurnal and stress related corticosterone levels with higher levels of corticosteroid-binding globulin in plasma, spleen and thymus than LEW or Sprague-Dawley rats (Dhabhar et al, 1993). Higher concentrations of cortical and hippocampal 5-HT1A receptors compared with LEW rats (Burnet et al, 1994). Hippocampal neurones are more vulnerable to ishemic insult than those of other strains (1/3) (Iwasaki et al, 1995).
Anderson A. E. (1982) Phenylketonuria, supplemental update to model not 47, in Handbook: Animal Models of Human Disease, Fascicle 11 ed. (Capen C. C., Hackel D. B., Jones T. C., and Migaki G., eds) Registry of Comparitive Pathology, Armed Forces Institute of Pathology, Washington, DC. \par
Bosland M. C., Prinsen M. K., Rivenson A., Silverman J., Fiala E., Williams G. M., Kroes R., and Weisburger J. H. (1992a) Induction of proliferative lesions of ventral prostate, seminal- vesicle, and other accessory sex glands in rats by N-methyl-N- nitrosourea - effect of castration, pretreatment with cyproterone- acetate and testosterone propionate, and rat strain. Prostate 20, 339-353. \par
Bosland M. C., Prinsen M. K., Rivenson A., and Weisburger J. H. (1992b) Induction of skin and thyroid-tumors in male-rats by normal-methyl- normal-nitrosourea after sequential treatment with cyproterone- acetate and testosterone propionate - effects of castration, rat strain and time of carcinogen injection. Carcinogenesis 13, 669-674. \par
Breslin P. A. S., Spector A. C., and Grill H. J. (1995) Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 38, R350-R356. \par
Burnet P. W. J., Michelson D., Smith M. A., Gold P. W., and Sternberg E. M. (1994) The effect of chronic imipramine administration on the densities of 5-HT1a and 5-HT2 receptors and the abundancies of 5-HT receptor and transporter messenger-RNA in the cortex, hippocampus and dorsal raphe of 3 strains of rat. Brain Res. 638, 311-324. \par
Cameron T. P., Hickman R. L., Kornreich M. R., and Tarone R. E. (1985) History, survival, and growth patterns of B6C3F1 mice and F344 rats in the National Cancer Institute carcinogenesis testing program. Fundam. Appl. Toxicol. 5, 526-538. \par
Carthew P., Rich K. J., Martin E. A., De Matteis F., Lim C.-K., Manson M. M., Festing M. F. W., White I. N. H., and Smith L. L. (1995) DNA damage as assessed by 32P-postlabelling in three rat strains exposed to dietary tamoxifen: the relationship between cell proliferation and liver tumour formation. Carcinogenesis 16, 1299-1304. \par
Cremer M. A., Terato K., Watson W. C., Griffiths M. M., Townes A. S., and Kang A. H. (1992) Collagen-induced arthritis in rats - examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type-II collagens. J. Immunol. 149, 1045-1053. \par
Dent J. G., Graichen M. E., Schnell S., and Lasker J. (1980) Constitutive and induced hepatic microsomal cytochrome P-450 monooxygenase activities in male Fischer-344 rats and CD rats. A comparative study. Toxicol. Appl. Pharmacol. 52, 45-53. \par
Dhabhar F. S., McEwen B. S., and Spencer R. L. (1993) Stress-response, adrenal-steroid receptor levels and corticosteroid- binding globulin levels - a comparison between Sprague-Dawley, Fischer-344 and Lewis rats. Brain Res. 616, 89-98. \par
Diloreto D., Cox C., Grover D. A., Lazar E., Delcerro C., and Delcerro M. (1994) The influences of age, retinal topography, and gender on retinal degeneration in the Fischer-344 rat. Brain Res. 647, 181-191. \par
English J. C., Perry L. G., Vlaovic M., Moyer C., and Odonoghue J. L. (1994) Measurement of cell-proliferation in the kidneys of Fischer-344 and Sprague-Dawley rats after gavage administration of hydroquinone. Fundam. Appl. Toxicol. 23, 397-406. \par
Faktorovich E. G., Steinberg R. H., Yasumura D., Matthes M. T., and Lavail M. M. (1992) Basic fibroblast growth-factor and local injury protect photoreceptors from light damage in the rat. Journal of Neuroscience 12, 3554-3567. \par
Gold G. and Widnell C. C. (1975) Response of NADPH cytochrome c reductase and cytochrome P-450 in hepatic microsomes to treatment with phenobarbital--Differences in rat strains. Biochem. Pharmacol. 24, 2106. \par
Gordon C. J. and Watkinson W. P. (1995) Strain differences in the laboratory rat - impact on the autonomic, behavioral, and biochemical response to cholinesterase inhibition. J. Toxicol. Environ. Health 45, 59-73. \par
Guitart X., Beitnerjohnson D., Marby D. W., Kosten T. A., and Nestler E. J. (1992) Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse 12, 242-253. \par
Hoffman H. J. (1979) Survival distributions for selected laboratory rat strains and stocks, in Development of the rodent as a model system for aging, Book II ed. (Gibson D. C., Adelman R. C., and Finch C., eds), pp. 19-34. DREW Pub. No. (NIH) 79-161, Washington, DC. (Department of Health, Education, and Welfare; Washington, D.C.: U.S.) \par
Iwasaki H., Ohmachi Y., Kume E., and Krieglstein J. (1995) Strain differences in vulnerability of hippocampal-neurons to transient cerebral-ischemia in the rat. International Journal of Experimental Pathology 76, 171-178. \par
Jia Y. L., Xu L. J., Heisler S., and Martin J. G. (1995) Airways of a hyperresponsive rat strain show decreased relaxant responses to sodium-nitroprusside. American Journal of Physiology-Lung Cellular and Molecular Physiology 13, L85-L91. \par
Joos G. F., Kips J. C., and Pauwels R. A. (1994) In-vivo characterization of the tachykinin receptors involved in the direct and indirect bronchoconstrictor effect of tachykinins in 2 inbred rat strains. American Journal of Respiratory and Critical Care Medicine 149, 1160-1166. \par
Ketchum R. J., Moore W. V., and Hegre O. D. (1992) Increased islet allograft survival after extended culture by a mechanism other than depletion of donor apcs - lack of correlation between the elimination of donor MHC class-II-positive accessory cells and increased transplantability. Transplant. 54, 347-351. \par
Lehman T. J. A., Allen J. B., Plotz P. H., and Wilder R. L. (1984) Lactobacillus-casei cell wall-induced arthritis in rats. Cell-wall fragment distribution and persistence in chronic arthritis-susceptible LEW/N and arthritis-resistant F344/N rats. Arthritis Rheum. 27, 939-942. \par
Milman H. A., Peckham J. C., Ward J. M., and Tyranny R. E. (1979) Reduction of the severity of nephropathy in aging Fischer 344 rats treated with analogs of arylsulfonylurea. Toxicol. Appl. Pharmacol. 49, 425-430. \par
Pan L. C., Wilson D. W., and Segall H. J. (1993) Strain differences in the response of Fischer-344 and Sprague-Dawley rats to monocrotaline induced pulmonary vascular-disease. Toxicology 79, 21-35. \par
Sass B., Rabstein L. S., Madison R., Nims R. M., Peters R. L., and Kelloff G. J. (1975) Incidence of spontaneous neoplasms in F344 rats throughout natural life-span. J. Natl. Cancer Inst. 54, 1449-1456. \par
Shibutani M., Maekawa A., Okeda R., Mitsumori K., Imazawa T., Yoshida J., Onodera H., and Hayashi Y. (1993) An experimental-model for anaplastic astrocytomas and glioblastomas using adult F344 rats and N-methyl-N-nitrosourea. Acta Pathologica Japonica 43, 464-474. \par
Shirai T., Nakamura A., Fukushima S., Yamamoto A., Tada M., and Ito N. (1990) Different carcinogenic responses in a variety of organs, including the prostate, of five different rat strains given 3,2'-dimethyl-4-aminobiphenyl. Carcinogenesis 11, 793-797. \par
Takahara E., Nagata O., Kato H., Ohta S., and Hirobe M. (1993) Interindividual differences of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid ((+)-mppb) disposition in rats. Biol. Pharmaceut. Bull. 16, 1057-1059. \par
Tanaka T., Kojima T., Kawamori T., Wang A. J., Suzui M., Okamoto K., and Mori H. (1993) Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally-occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. Carcinogenesis 14, 1321-1325. \par
Tanase H., Yamori Y., Hansen C. T., and Lovenberg W. (1982) Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats. Hypertension 4, 864-872. \par
Vandelangerijt A. G. M., Vanlent P. L. E. M., Hermus A. R. M. M., Vandeputte L. B. A., and Vandenberg W. B. (1993) Regulation of resistance against adjuvant arthritis in the Fisher rat. Clin. Exp. Immunol. 94, 150-155. \par
Witkin J. M. and Goldberg S. R. (1992) Effects of D-amphetamine, Win-35,428, pentobarbital and morphine on schedule-controlled responding in 2 inbred rat strains that differ in locomotor stimulatory effects of cocaine. Behavioural Pharmacology 3, 455-463. \par
Yu B. P., Masoro E. J., Murata I., Bertrand H. A., and Lynd F. T. (1982) Life span study of SPF Fischer 344 male rats fed ad libitum or restricted diets: Longevity, growth, lean body mass and disease. J. Gerontol. 37, 130-141. \par
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