WKY/N

Colour: Albino,

Genet. a, B, c, h, P, R

Origin: National Institutes of Health in 1971 from outbred Wistar stock from Kyoto School of Medicine. Inbred as a normotensive control strain for SHR (Hanesn et al 1973), though there is some controversy about the validity of such use (see Rapp 1987). Johnson et al (1992) found large genetic differences using restriction fragment length polymorphisms between WKY and SHR, comparable to the maximum divergence possible between unrelated humans. Also, breeding stock of ths strain was distributed before F20, possibly resulting in the emergence of a number of strains or substrains (Kurtz and Morris 1987, Kurtz et al 1989). It is therefore essential that subline codes are always used in designating this strain.

Characteristics:

Some demonstrate heritable biventricular cardiac hypertrophy, providing a model of volume-load hypertrophy (Pfeiffer et al 1979 using breeding stock obtained from the NIH in 1973 at F5). Similarly, Kuribayashi et al (1988) found a high incidence of a range of cardiac abnormalities in WKY/NCrj substrain rats. Belledonne et al (1979) showed that WKY/Tac rats are sensitive to sodium chloride-induced hypertension and have abnormal acid and ammonium excretion. Sensitive to the induction of ulcers by stress (1/4) (Pare 1989). Hyperresponsive to a novel environment as indicated by delay in entering the open field, increased grooming, reduced rearing, and reduced locomotion. Plasma ACTH levels were found to be 67% higher than in BN rats, with an inverse correlation with longevity (Tizabi et al, 1992, Gilad et al, 1993). Relatively sensitive to the induction of experimental autoimmune glomerulonephritis (1/4, cf F344)(Sado et al 1986). Like the COP strain, resistant to the development of induced and spontaneous mammary carcinomas due to one homozygous copy of a mammary tumour suppressor gene (Haag et al 1992). Resistant to the induction of glandular stomach adenocarcinomas following treatment with catechol (contrast LEW, Wistar and Sprague-Dawley) (Tanaka et al, 1995)

Compared with SHR/N, ACI and F344/N, has low levels of cytochrome Cyp2C11 but relatively high levels of S-warfarin 4-and 8-hydroxylase activities (Kitareewan and Walz, 1994). Epitope specificities of collagen-induced arthritis studied by Cremer et al (1992). Resistant to the development of mammary carcinomas (both spontaneous and induced) due to a suppressor gene which appears to be similar or identical to that carried by strain COP. However, WKY also carries one or more susceptibility genes (Haag et al 1992).

Low 10-week body weight in males (4/23) (Tanase et al 1982). Bellhorn et al (1987) found that rats of the substrain maintained by Charles River Inc. develop an outer retinal degeneration by middle age.

A congenic strain carrying the fatty gene (fa) (N8-N10) has been described by Peterson et al (1990a). It appears in many ways to be similar to strain WDF/Ta-fa, with non-insulin-dependent diabetes mellitus.

Slow acetylator due to polymorphism of N-acetyltransferase (like NSD but contrast PETH) (Juberg et al, 1991)

Bellhorn R. W., Rheinhardt J. M., Burns M. S., and Matthes M. T. (1987) Retinal degeneration in the WKY rat. Degenerative Retinal Disorders: Clin. and Laboratory Invests. 317-331. Liss, Inc, Alan R.

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.

Gilad G. M., Li R., Wyatt R. J., and Tizabi Y. (1993) Effects of genotype on age-related alterations in the concentrations of stress hormones in plasma and hypothalamic monoamines in rats. J. Reprod. Fertil. S46, 119-130.

Johnson M. D. and Richmond B. K. (1992) Effect of naloxone on hypertension in Dahl salt-sensitive rats. Am. J. Physiol. 262, H162-H167.

Juberg D. R., Bond J. T., and Weber W. W. (1991) N-acetylation of aromatic-amines - genetic-polymorphism in inbred rat strains. Pharmacogenetics 1, 50-57.

Kitareewan S. and Walz F. G. (1994) Genetic and developmental diversity of hepatic cytochromes-P450 -warfarin and progesterone metabolism by hepatic microsomes from 4 inbred strains of rat. Drug Metab. Disp. 22, 607-615.

Kuribayashi Y., Mizuta T., Shimoo K., Kubota K., Katsume H., Nakagawa M., and Ibata Y. (1988) Spontaneously occurring hypertrophic cardiomyopathy in the rat. Jpn. Circ. J. 52, 1156-1170.

Kurtz T. W. and Morris R. C. Jr. (1987) Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension 10, 127-131.

Kurtz T. W., Montano M., Chan L., and Kabra P. (1989) Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat. Hypertension 13, 188-192.

Pare W. (1989) Strain, age, but not gender, influence ulcer severity induced by water-restraint stress. Physiol. Behav. 45, 627-632.

Peterson R. G., Little L. A., and Neel M.-A. (1990a) WKY fatty rat as a model of obesity and non-insulin-dependent diabetes mellitus. ILAR News 32, 13-15.

Rapp J. P. (1987) Use and misuse of control strains for genetically hypertensive rats. Hypertension 10, 7-10.

Sado Y., Naito I., Akita M., and Okigaki T. (1986) Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis. J. Clin. Lab. Immunol. 19, 193-199.

Tanaka H., Hirose M., Hagiwara A., Imaida K., Shirai T., and Ito N. (1995) Rat strain differences in catechol carcinogenicity to the stomach. Food and Chemical Toxicology 33, 93-98.

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.

Tizabi Y., Aguilera G., and Gilad G. M. (1992) Age-related reduction in pituitary corticotropin-releasing hormone receptors in 2 rat strains. Neurobiology of Aging 13, 227-230.