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Somatic Cell and Molecular Genetics

, Volume 20, Issue 2, pp 87–97 | Cite as

Mouse Huntington's disease gene homolog (Hdh)

  • Glenn T. Barnes
  • Mabel P. Duyao
  • Christine M. Ambrose
  • Sandra McNeil
  • Francesca Persichetti
  • Jayalakshmi Srinidhi
  • James F. Gusella
  • Marcy E. MacDonald
Article

Abstract

The incurable neurodegenerative disorder, Huntington's disease (HD), is caused by an expanded, unstable CAG repeat encoding a stretch of polyglutamine in a 4p16.3 gene (HD) of unknown function. Near the CAG repeat is a polyproline-encoding CCG repeat that shows more limited allelic variation. The mouse homologue,Hdh, has been mapped to chromosome 5, in a region devoid of mutations causing any comparable phenotype. We have isolated overlapping cDNAs from theHdh gene and compared their sequences with the human transcript. The consensus mouse coding sequence is 86% identical to the human at the DNA level and 91% identical at the protein level. Despite the overall high level of conservation,Hdh possesses an imperfect CAG repeat encoding only seven consecutive glutamines, compared to the 13–36 residues that are normal in man. Although no evidence for polymorphic variation of the CAG repeat was seen, a nearby CCG repeat differed in length by one unit between several strains of laboratory mouse andMus spretus. The absence of a long CAG repeat in the mouse is consistent with the lack of a spontaneous mouse model of HD. The information presented concerning the sequence of the mouse gene should facilitate attempts to create such a model.

Keywords

Mouse Gene Polymorphic Variation Laboratory Mouse Mouse Homologue Human Transcript 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Glenn T. Barnes
    • 1
    • 2
  • Mabel P. Duyao
    • 1
    • 2
  • Christine M. Ambrose
    • 1
    • 2
  • Sandra McNeil
    • 1
    • 2
  • Francesca Persichetti
    • 1
    • 2
  • Jayalakshmi Srinidhi
    • 1
    • 2
  • James F. Gusella
    • 1
    • 2
  • Marcy E. MacDonald
    • 1
    • 2
  1. 1.Molecular Neurogenetics UnitMassachusetts General HospitalCharlestown
  2. 2.Department of GeneticsHarvard Medical SchoolBoston

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