Zeitlin S, Liu J P, Chapman D L, Papaioannou V E, Efstratiadis A
Department of Pathology, Columbia University, New York, New York 10032, USA.
Nat Genet. 1995 Oct;11(2):155-63. doi: 10.1038/ng1095-155.
The expansion of CAG triplet repeats in the translated region of the human HD gene, encoding a protein (huntingtin) of unknown function, is a dominant mutation leading to manifestation of Huntington's disease. Targeted disruption of the homologous mouse gene (Hdh), to examine the normal role of huntingtin, shows that this protein is functionally indispensable, since nullizygous embryos become developmentally retarded and disorganized, and die between days 8.5 and 10.5 of gestation. Based on the observation that the level of the regionalized apoptotic cell death in the embryonic ectoderm, a layer expressing the Hdh gene, is much higher than normal in the null mutants, we propose that huntingtin is involved in processes counterbalancing the operation of an apoptotic pathway.
