Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif.

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight. The affected rats showed a high lethality and histological changes of the liver with focal necrosis of enlarged hepatocytes without inflammatory cell response. Genetic tests indicate that at least a single autosomal recessive gene is responsible for the major cause of hepatitis. Furthermore, liver cancer appears in long survived rats after recovery from jaundice as well as a few asymptomatic rats without jaundice. The LEC rats thus provide an animal model useful for the basic and clinical studies of hepatitis and liver cancer, including their pathogenesis, prevention, and treatment.

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