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We investigated LEC rats immunopathologically which spontaneously developed hepatitis to find out the genesis, in comparison with non-hepatitis LEA (Long Evans Agouti) rats. 1) Wet weights of the spleen and thymus of 6-week old LEC rats were significantly lighter than those of LEA rats of the same age. 2) Serum IgG (Immunoglobulin G) in LEC rats remained markedly low after the age of two months and IgG antibody formation to SRBC (Sheep Red Blood Cell) as detected by plaque assay was also significantly suppressed. On the other hand, IgM antibody formation to SRBC was significantly suppressed through serum IgM level in LEC rats was normal or rather increased. 3) Blastogenic responses of spleen cells to PHA and Con A were much more suppressed in LEC rats than in LEA rats. 4) Cytostatic activity of intraperitoneal macrophages against tumor cells was more evident in LEC rats than in LEA rats, but there was no difference in NK (natural killer) activity between the two rat strains. From these results, it is speculated that spontaneously hepatitis-developing LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activities are linked to the genesis of developing hepatitis.

At the Center for Experimental Plants and Animals, Hokkaido University, two inbred strains, Long Evans Cinnamon (LEC) and Long Evans Agouti (LEA), which were selected for coat colour, were isolated from a closed colony of Long Evans rats. While the two inbred strains were maintained by sibmating, only LEC rats, over 24-generation, spontaneously developed acute hepatitis with sudden appearance of systemic jaundice at around four months after birth. The frequency of acute hepatitis was 80 to 90% and the disease in nearly 80% of these rats were progressive and they died within two weeks after onset, with their clinical course and histopathological findings similar to those of human fulminant hepatitis. LEC rats with spontaneous hepatitis had strong-conversion of urine-bilirubin, ultimate increase of blood-bilirubin and abnormal increase of serum-transaminases (GOT, GPT; GOT greater than GPT). Histopathological findings of the livers in the rats with acute hepatitis showed spotty necrosis and abnormal hepatocytes containing giant bizarre nuclei and in the rats with fulminant-type hepatitis showed central or coagulated necrosis and marked infiltration of inflammatory cells. Serum levels of albumin in LEC rats before being affected by hepatitis were low compared with those of LEA rats and especially characteristic fact was that cellulose-acetate electrophoresis could not reveal gamma-globulin fraction in LEC rats of 6-week and 12-week old, which will be a clue to analyze the etiology of hepatitis in LEC rats.

We have reported an inbred strain LEC rats with high frequency of spontaneous hepatitis. In this paper, we study a possible involvement of hepatitis virus, hereditary background, and correlation between serum IgG level and onset of hepatitis in LEC rats. Neither electron microscopy nor indirect immunofluorescent test could detect hepatitis virus article or antigen. Furthermore, we could not succeed in inducing hepatitis of LEA and WKA/H rats by injecting the serum, plasma and liver homogenates of the affected IEC rats, nor in promoting/developing hepatitis of LEC and LEA rats under the immunosuppressed condition by administration of steroid hormone. When we made a mating between LEC and non-hepatitis rats to investigate the hereditary mode, F1s had no hepatitis, but F2s and backcrosses developed hepatitis. We observed, in particular, the lower the serum IgG level was, the higher the rate of developing hepatitis was. From these results, we speculate that the involvement of hepatitis virus is not likely, but that a genetic mutation might cause low level of IgG and be also correlated with development of hepatitis.