References
Query Results -- Details
MGI Accession ID: MGI:1333422
J Number: J:53797
Other Accession IDs:
Title: Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin [published erratum appears in Hum Mol Genet 1999 May;8(5):943]
Authors: Schilling G; Becher MW; Sharp AH; Jinnah HA; Duan K; Kotzuk JA; Slunt HH; Ratovitski T; Cooper JK; Jenkins NA; Copeland NG; Price DL; Ross CA; Borchelt DR
Journal: Hum Mol Genet
Volume: 8
Issue: 3
Date: 1999 Mar
Year: 1999
Pages: 397-407
Review Status: Peer Reviewed
Abstract:
Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein. To gain insight into the patho-genesis of HD, we generated transgenic mice that express a cDNA encoding an N-terminal fragment (171 amino acids) of huntingtin with 82, 44 or 18 glutamines. Mice expressing relatively low steady-state levels of N171 huntingtin with 82 glutamine repeats (N171-82Q) develop behavioral abnormalities, including loss of coordination, tremors, hypokinesis and abnormal gait, before dying prematurely. In mice exhibiting these abnormalities, diffuse nuclear labeling, intranuclear inclusions and neuritic aggregates, all immunoreactive with an antibody to the N-terminus (amino acids 1-17) of huntingtin (AP194), were found in multiple populations of neurons. None of these behavioral or pathological phenotypes were seen in mice expressing N171-18Q. These findings are consistent with the idea that N-terminal fragments of huntingtin with a repeat expansion are toxic to neurons, and that N-terminal fragments are prone to form both intranuclear inclusions and neuritic aggregates.
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