Hydrocephalus in the H-Tx rat: A monogenic disease?

The H-Tx rat is a genetic model of hydrocephalus for which there is a poor understanding of the mode of inheritance. Previous studies suggested a poly genic mode of inheritance but the breeding data to support this hypothesis have not been reported. In an attempt to clarify the hereditary mode we hav e analyzed the data from eight generations of H-Tx rats and four generation s of cross-matings between H-Tx rats and Sprague-Dawley (SD) rats. In the H -Tx rat colony 113 of 129 random brother-sister matings (87.60%) produced h ydrocephalic offspring, with males and females being equally affected. The overall incidence varied greatly with an average of 30.35%. In matings with more than three litters, all mating pairs yielded hydrocephalic pups. In c ross-matings both hydrocephalic and normal H-Tx rats were mated with normal SD rats. No hydrocephalus was observed in the first generation of 124 pups (F1). Subsequent brother-sister matings of F1 animals generated hydrocepha lic pups in the F2 generation with a lower incidence (4.67% in hydrocephali c HTx/SD matings and 5.11% in normal HTx/SD matings, respectively) than in the II-Tx rat colony (30.35%). Back-cross-matings between F2 rats and norma l H-TK rats yielded an incidence of hydrocephalus higher than that of the c ross-matings but lower than that of the II-Tx colony. These data strongly s uggest that the II-Tx rat is a homozygous carrier of an autosomal recessive hydrocephalus gene with incomplete penetrance. Furthermore, the data clear ly rule out sex-linked and polygenic modes of inheritance and provide furth er insight with respect to genetic inheritance of hydrocephalus. (C) 2000 A cademic Press.