Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice.
Inactivation of the mouse homologue of the Huntington disease gene (Hdh) results in early embryonic lethality. To investigate the normal function of Hdh in the adult and to evaluate current models for Huntington disease (HD), we have used the Cre/loxP site-specific recombination strategy to inactivate Hdh expression in the forebrain and testis, resulting in a progressive degenerative neuronal phenotype and sterility. On the basis of these results, we propose that huntingtin is required for neuronal function and survival in the brain and that a loss-of-function mechanism may contribute to HD pathogenesis.
Dragatsis
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I
Department of Genetics and Development, Columbia University, New York, New York, USA.
Levine
M S
MS
Zeitlin
S
S
D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018390:Gene Targeting; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D000071058:Huntingtin Protein; D007248:Infertility, Male / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D014764:Viral Proteins
D005904:Glial Fibrillary Acidic Protein; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases