The expression of inherited hydrocephalus in H-Tx rats

OBJECTIVES: H-Tx rats develop severe hydrocephalus in late gestation. The breeding colony maintained at the University of Florida stems from one pair obtained in 1992. The aims of this study were to characterize the expression of hydrocephalus in the H-Tx rat colony, to perform within-strain and between-strain DNA analysis and to examine hydrocephalus expression in specific breeding experiments.

METHODS AND OBSERVATIONS: Matings between normal rats produce hydrocephalic offspring almost without exception, and the overall frequency is stable between generations at 40%. However, frequency varies with parity, being only 27% in the first litters, and it also varies with sex, there being an excess of male hydrocephalics. Mating between shunt-treated hydrocephalic rats did not increase the frequency. DNA typing with microsatellite markers showed that there was some residual heterogeneity in the colony despite inbreeding for 22 generations, although it did not segregate with hydrocephalus. Test mating with two other inbred strains, F344 and LEW produced some affected pups in the LEW cross only. A backcross experiment between H-Tx and F344 produced 12.3% severely-affected pups and 5.4% pups with a mild form, indicating the presence of several susceptibility genes.

CONCLUSIONS: All animals in our H-Tx colony are homozygous for the hydrocephalus loci, but there is incomplete penetrance.