Premature death and neurologic abnormalities in transgenic mice expressing a mutant huntingtin exon-2 fragment.
Premature death and neurologic abnormalities in transgenic mice expressing a mutant huntingtin exon-2 fragment.
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DOI：
10.1093/hmg/ddr040
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发表时间：
2011-04-15
影响因子：
3.5
通讯作者：
Borchelt DR
中科院分区：
文献类型：
--
作者：
Tebbenkamp AT;Swing D;Tessarollo L;Borchelt DR
Huntington's disease (HD) is a fatal neurodegenerative disease characterized pathologically by aggregates composed of N-terminal fragments of the mutant form of the protein huntingtin (htt). The role of these N-terminal fragments in disease pathogenesis has been questioned based in part on studies in transgenic mice. In one important example, mice that express an N-terminal fragment of mutant htt terminating at the C-terminus of exon 2 (termed the Shortstop mouse) were reported to develop robust inclusion pathology without developing phenotypic abnormalities seen in the R6/2 or N171-82Q models of HD, which are also based on expression of mutant N-terminal htt fragments. To further explore the capacity of mutant exon-2 htt fragments to produce neurologic abnormalities (N-terminal 118 amino acids; N118), we generated transgenic mice expressing cDNA that encodes htt N118-82Q with the mouse prion promoter vector. In mice generated in this manner, we demonstrate robust inclusion pathology accompanied by early death and failure to gain weight. These phenotypes are the most robust abnormalities identified in the R6/2 and N171-82Q models. We conclude that the lack of an overt phenotype in the initial Shortstop mice cannot be completely explained by the properties of mutant htt N118 fragments.
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DOI：
10.1083/jcb.141.5.1097
发表时间：
1998-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hackam AS;Singaraja R;Wellington CL;Metzler M;McCutcheon K;Zhang T;Kalchman M;Hayden MR
通讯作者：
Hayden MR
DOI：
10.1016/s1050-3862(96)00167-2
发表时间：
1996-12-01
期刊：
GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Borchelt, DR;Davis, J;Price, DL
通讯作者：
Price, DL
影响因子：
15.8
作者：
Jankowsky JL;Slunt HH;Gonzales V;Savonenko AV;Wen JC;Jenkins NA;Copeland NG;Younkin LH;Lester HA;Younkin SG;Borchelt DR
通讯作者：
Borchelt DR
影响因子：
4.8
作者：
Landles, Christian;Sathasivam, Kirupa;Bates, Gillian P.
通讯作者：
Bates, Gillian P.
影响因子：
9.9
作者：
MYERS, RH;VONSATTEL, JP;BIRD, ED
通讯作者：
BIRD, ED