Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion.

Nature genetics | Dec 29, 1997

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a CAG repeat expansion that lengthens a glutamine segment in the novel huntingtin protein. To elucidate the molecular basis of HD, we extended the polyglutamine tract of the mouse homologue, Hdh, by targetted introduction of an expanded human HD CAG repeat, creating mutant HdhneoQ50 and HdhQ50 alleles that express reduced and wild-type levels of altered huntingtin, respectively. Mice homozygous for reduced levels displayed characteristic aberrant brain development and perinatal lethality, indicating a critical function for Hdh in neurogenesis. However, mice with normal levels of mutant huntingtin did not display these abnormalities, indicating that the expanded CAG repeat does not eliminate or detectably impair huntingtin's neurogenic function. Thus, the HD defect in man does not mimic complete or partial Hdh inactivation and appears to cause neurodegenerative disease by a gain-of-function mechanism.

Pubmed ID: 9398841 RIS Download

Mesh terms: Alleles | Animals | Cell Differentiation | Embryonic and Fetal Development | Gene Deletion | Heterozygote | Homozygote | Humans | Huntingtin Protein | Huntington Disease | Male | Mice | Mice, Mutant Strains | Mice, Transgenic | Mutagenesis, Insertional | Nerve Tissue Proteins | Nuclear Proteins | Phenotype | Repetitive Sequences, Nucleic Acid

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: NS16367
  • Agency: NINDS NIH HHS, Id: NS32765

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.