Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue.
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.
Pubmed ID: 7550343 RIS Download
Animals | Apoptosis | Base Sequence | Blastocyst | Chimera | DNA Primers | Embryo, Mammalian | Fetal Death | Genes, Dominant | Genes, Lethal | Genotype | HeLa Cells | Humans | Huntingtin Protein | Huntington Disease | Kidney | Mice | Molecular Sequence Data | Nerve Tissue Proteins | Nuclear Proteins | Polymerase Chain Reaction | Protein Biosynthesis | Reference Values | Repetitive Sequences, Nucleic Acid | Restriction Mapping | Stem Cells