Huntington's disease: Translating a CAG repeat into a pathogenic mechanism

Current Opinion in Neurobiology

Volumn 6, Issue 5, 1996, Pages 638-643

  MacDonald, Marcy E ^a   Gusella, James F ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GENE PRODUCT; TRINUCLEOTIDE;

AMINO ACID SEQUENCE; CELL DEATH; GENE MUTATION; HUMAN; HUNTINGTON CHOREA; NERVE CELL; PRIORITY JOURNAL; SHORT SURVEY;

EID: 0030273702     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(96)80097-3     Document Type: Article

References (45)

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29. of special interest Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, Ge P, Vonsattel JP, Gusella JF, Joyner AL, MacDonald ME. Inactivation of the mouse Huntington's disease gene homolog Hdh. Science. 269:1995;407-410 Use of gene targeting to completely inactive the Hdh gene by removing both exons 4 and 5. In contrast to [28], this mutant allele produces no protein and causes no heterozygous phenotype. Homozygote mutant mice die at about embryonic day 7.5, before emergence of the neural tube, demonstrating that huntingtin is essential early in normal development but that complete elimination of huntingtin is not cell lethal.
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34. 2+-dependent manner) the interaction of huntingtin with calmodulin and other findings related to huntingtin's biochemical properties in non-denaturing conditions.
35. of special interest Li X-J, Li S-H, Sharp AH, Nucifora JC Jr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA. A huntingtin-associated protein enriched in brain with implications for pathology. Nature. 378:1995;398-402 Reports a novel protein found in brain that interacts with the amino terminus of huntingtin in a yeast two-hybrid system in a glutamine-length-dependent manner. Importantly, HAP1 can also be co-immunoprecipitated with huntingtin from HD brains.
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37. of special interest Li X-J, Sharp AH, Li S-H, Dawson RM, Snyder SH, Ross CA. Huntingtin associated protein (HAP1): discrete neuronal localizations in the brain resemble neuronal nitric oxide synthase. Proc Natl Acad Sci USA. 1996; Reports the distribution of HAP1 in brain, raising the possibility that it is involved with neuronal nitric oxide synthase related activities in the cell.
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41. of special interest Gusella JF, MacDonald ME. Pathogenic mechanism in Huntington's disease. Cold Spring Harb Symp Quant Biol. 1996; Finds that the pathogenic mechanisms in HD, SBMA, SCA1 are probably different than those operating in DRPLA and MJD, on the basis of the inverse correlation between CAG repeat length and age at death or age at onset in each of these disease for heterozygotes and homozygotes.
42. of outstanding interest Kawakami H, Maruyama H, Nakamura S, Kawaguchi Y, Kakizuka A, Doyu M, Sobue G. Unique features of the CAG repeats in Machado-Joseph disease. Nature Genet. 9:1995;344-345 Reports that MJD1 homozygotes with two expanded MJD CAG alleles have a more severe disease with earlier onset of symptoms than do heterozygotes arguing that different mechanisms may be operating in HD and MJD.
43. Sato K, Kashihara K, Okada S, Ikeuchi T, Tsuji S, Shomori T, Morimoto K, Hayabara T. Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy? Neurology. 45:1995;1934-1936.
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