Genet: a, h, c.
Origin: Dr. Margaret Lewis from Wistar stock, to Aptekman and Bogden 1954 at F20, to Silvers in 1958 at F31. Subsequently distributed by Silvers. Used as the inbred partner for a number of congenic strains at the major histocompatibility complex (Stark and Kren 1969). A substrain with congenital hydrocephalus due to primary aqueductal stenosis has been described by Yamada et al, (1992)
Moderately sensitive to the development of experimental glomerulonephritis following injection of nephritogenic antigen from bovine renal basement membrane (2/10) (Naito et al, 1991)
Susceptible to the induction of proteinuria following treatment with the monoclonal antibody 5-6-1, like BN and outbred Wistar, but unlike resistant outbred Sprague-Dawley rats which were also resistant to glomerular damage (Gollner et al, 1995).
A substrain (initially designated Le-R, but now re-named strain LER), resistant to the development of experimental allergic encephalomyelitis but which is still histocompatible with LEW has been described by Waxman et al (1981) and Driscoll et al (1985). Gasser et al (1983) suggested that the resistance is probably due to a non-MHC-linked mutation. However, it now seems that resistance is due to genetic contamination by BUF strain rats (Goldmuntz et al, 1993, see strain LER).
About half of females sensitised against H-Y antigen accept skin grafts from neonatal sygeneic males, and about half of these will subsequently accept skin from adult males (Silvers and Collins 1979). High antibody response to concanavalin A and phytohaemagglutinin (Williams et al 1973). Interferon production in response to polyriboinosinic-polyribocytodilic acid 20-40 fold higher than that observed in six other inbred strains. The effect is due to more than one gene, and is not associated with the MHC (Davis et al 1984). Resident macrophages (ramified microglea) of the central nervous system are not constitutively major histocompatibility complex class-II positive, in contrast with BN (Sedgwick et al, 1993). Mercury (HgCl2) stimulates peritoneal polymorphonuclear leukocytes and macrophages to produce hydrogen peroxide, in contrast with strain BN (Contrino et al, 1992). Resistant to the development of autoimmunity from skin-injected HgCl2 , in contrast to BN (Warfvinge and Larsson, 1994). Poor (5/5) antibody response to a synthetic 20 amino acid peptide derived from the alpha helical region of the RT1-D-u beta chain (Murphy et al, 1994). Although DA and LEW are both highly susceptible to the development of EAE, there are marked differences in the array of myelin epitopes capable of inducing the disease as well as MHC restriction of these epitopes between the two strains (Stepaniak et al, 1995).
Highly susceptible to inflammatory disease due to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone responsiveness. Have significantly more benzodiazepine binding sites than F344, though there was no difference in affinities (Smith et al, 1992 see also Oitzl et al, 1995). No differences between LEW and F344 in the sensitivity of target tissues to exogenous glucocorticoids which could be associated with differences in susceptibility to inflammatory disease (Karalis et al, 1995).
Biochemistry and Physiology
High fertility. High serum thyroxine, insulin and growth hormone levels (1/5 in each case) (Esber et al 1974). Becomes obese on a high fat diet (rank 2/7)(Schemmel et al 1970). High hepatic metabolism of ethylmorphine in females (3/10) (Page and Vesell 1969). Short gestation period (3/8) (Peters 1986). Low blood pressure (22/23), reaching 119_2.0 (SEM) mmHg at 10 weeks of age (Tanase et al 1982). Liver gangliosides are of the a-type (cf ACI, LEA, & BUF) (Kasai et al 1993). Rapid metaboliser of MPPB (F344 is slow) (Takahara et al 1993). Have substantially lower levels of diurnal and stress related corticosterone levels with higher levels of corticosteroid-binding globulin in plasma, spleen and thymus than F344 rats (Dhabhar et al, 1993). Lower concentrations of cortical and hippocampal 5-HT1A receptors compared with F344 and outbred Spargue-Dalwey rats (Burnet et al, 1994).
Baum A., Pohlmeyer G., Rapp K. G., and Deerberg F. (1995) Lewis rats of the inbred strain LEW/Han - life expectancy, spectrum and incidence of spontaneous neoplasms. Experimental and Toxicologic Pathology 47, 11-18. \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
Clark R. L., Cuttino J. T., Anderle S. R., Cromartie W. J., and Schwab J. H. (1979) Radiologic analysis of arthritis in rats after systemic injection of streptococcal cell walls. Arthritis Rheum. 22, 25-35. \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
Davis C. T., Blankenhorn E. P., and Murasko D. M. (1984) Genetic variaion in the ability of several strains of rats to produce interferon in response to polyriboinosinic-polyribocytodilic acid. Infect. Immun. 43, 580-583. \par
Dekozak Y., Naud M. C., Bellot J., Faure J. P., and Hicks D. (1994) Differential tumor-necrosis-factor expression by resident retinal cells from experimental uveitis-susceptible and uveitis-resistant rat strains. J. Neuroimmunol. 55, 1-9. \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
Goldmuntz E. A., Wilder R. L., Goldfarb Y., Cash J. M., Zha H. B., Crofford L. J., Mathern P., Hansen C. T., and Remmers E. F. (1993) The origin of the autoimmune disease-resistant LER rat - an outcross between the Buffalo and autoimmune disease-prone Lewis inbred rat strains. J. Neuroimmunol. 44, 215-219. \par
Gollner D., Kawachi H., Oite T., Oka M., Nagase M., and Shimizu F. (1995) Strain variation in susceptibility to the development of monoclonal- antibody 5-1-6-induced proteinuria in rats. Clin. Exp. Immunol. 101, 341-345. \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
Holmdahl R. and Kvick C. (1992) Vaccination and genetic experiments demonstrate that adjuvant-oil- induced arthritis and homologous type-II collagen-induced arthritis in the same rat strain are different diseases. Clin. Exp. Immunol. 88, 96-100. \par
Imrich H., Schwender S., Hein A., and Dorries R. (1994) Cervical lymphoid-tissue but not the central-nervous-system supports proliferation of virus-specific T-lymphocytes during coronavirus- induced encephalitis in rats. J. Neuroimmunol. 53, 73-81. \par
Kallen B. and Logdberg L. (1982) Low susceptibility to the induction of experimental autoimmune encephalomyelitis in a substrain of the otherwise susceptible Lewis rat. Eur. J. Immunol. 12, 596-599. \par
Karalis K., Crofford L., Wilder R. L., and Chrousos G. P. (1995) Glucocorticoid and/or glucocorticoid antagonist effects in inflammatory disease-susceptible Lewis rats and inflammatory disease- resistant Fischer rats. Endocrinol. 136, 3107-3112. \par
Kelchner J., McIntosh J. R., Beedecker E., Guggenheim S., and McIntosh R. M. (1976) Experimental autologous immune deposit nephritis in rats associated with mercuric chloride administration. Experientia 32, 1204-1208. \par
Koga T., Pearson C. M., Narita T., and Kotani S. (1973) Polyarthritis induced in the rat with cell walls from several bacteria and two Streptomyces species. Proc. Soc. Exp. Biol. Med. 143, 824-827. \par
Kosten T. A., Miserendino M. J. D., Chi S., and Nestler E. J. (1994) Fischer and Lewis rat strains show differential cocaine effects in conditioned place preference and behavioral sensitization but not in locomotor-activity or conditioned taste-aversion. J. Pharmacol. Exp. Therapeut. 269, 137-144. \par
Lehman T. J. A., Allen J. B., Plotz P. H., and Wilder R. L. (1983) Polyarthritis in rats following the systemic injection of Lactobacilus casei cell walls in aqueous suspension. Arthritis Rheum. 26, 1259-1265. \par
McFarlin D. E., Hsu S. C.-L., Slemenda S. B., Chou S. C.-H., and Kibler and R. F. (1975a) The immune response against an encephalitogenic fragment of guinea pig basic protein in the Lewis and Brown Norway strains of rat. J. Immunol. 115, 1456-1458. \par
Naito I., Kagawa M., Sado Y., and Okigaki T. (1991) Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis - presence of a broad- spectrum of the susceptibility. International Journal of Immunopathology and Pharmacology 4, 145-154. \par
Nicholls S. M., Benylles A., Shimeld C., Easty D. L., and Hill T. J. (1994) Ocular infection with herpes-simplex virus in several strains of rat. Investigative Ophthalmology & Visual Science 35, 3260-3267. \par
Oitzl M. S., Vanhaarst A. D., Sutanto W., and Dekloet E. R. (1995) Corticosterone, brain mineralocorticoid-receptors (MRS) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis - the lewis rat as an example of increased central MR-capacity and a hyporesponsive HPA-axis. Psychoneuroendocrinology 20, 655-675. \par
Perlik F. and Zideck Z. (1974) The susceptibility of several inbred strains of rats to adjuvant-induced arthritis and experimental allergic encephalomyelitis. Z. Immunitactsforsch. Exp. Klin. Immunol. 147, 191-193. \par
Sasamoto Y., Kotake S., Yoshikawa K., Wiggert B., Gery I., and Matsuda H. (1994) Interphotoreceptor retinoid-binding protein-derived peptide can induce experimental autoimmune uveoretinitis in various rat strains. Current Eye Research 13, 845-849. \par
Sedgwick J. D., Schwender S., Gregersen R., Dorries R., and Termeulen V. (1993) Resident macrophages (ramified microglia) of the adult Brown Norway rat central-nervous-system are constitutively major histocompatibility complex class-II positive. J. Exp. Med. 177, 1145-1152. \par
Smith C. C., Hauser E., Renaud N. K., Leff A., Aksentijevich S., Chrousos G. P., Wilder R. L., Gold P. W., and Sternberg E. M. (1992) Increased hypothalamic [H-3] flunitrazepam binding in hypothalamic pituitary-adrenal axis hyporesponsive Lewis rats. Brain Res. 569, 295-299. \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
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
Waxman F. J., Perryman L. E., Hinrichs D. J., and Coe J. E. (1981) Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis. J. Exp. Med. 153, 61-74. \par
Wilder R. L., Calandra G. B., Garvin A. J., Wright K. D., and Hansen C. T. (1982) Strain and sex variation in the susceptibility to streptococcal cell wall-induced polyarthritis in the rat. Arthritis Rheum. 25, 1064-1072. \par
Willenborg D. O. (1979) Experimental allergic encephalomyelitis in the Lewis rat: Studies on the mechanism of recovery from disease and acquired resistance to reinduction. J. Immunol. 123, 1145-1150. \par
Williams R. M., Moore M. J., and Benacerraf B. (1973) Genetic control of thymus-derived cell function. III. DNA synthetic responses of rat lymph node cells stimulated in culture with concanavalin A and phytohemagglutinin. J. Immunol. 111, 1571-1578. \par
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