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Mice carrying a R142C Notch 3 knock–in mutation do not develop a CADASIL‐like phenotype
Author(s) -
Lundkvist Johan,
Zhu Shunwei,
Hansson Emil M.,
Schweinhardt Petra,
Miao Qing,
Beatus Paul,
Dannaeus Karin,
Karlström Helena,
Johansson Clas B.,
Viitanen Matti,
Rozell Björn,
Spenger Christian,
Mohammed Abdul,
Kalimo Hannu,
Lendahl Urban
Publication year - 2005
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20091
Subject(s) - cadasil , leukoencephalopathy , missense mutation , notch signaling pathway , biology , mutation , phenotype , genetics , ectodomain , pathology , gene , medicine , disease , receptor
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, MIM 125310) is a genetic vascular dementia disease that is linked to missense mutations, small in‐frame deletions, and splice site mutations in the human Notch 3 gene. Here we describe the generation of a mouse knockin model for one of the most prevalent CADASIL mutations, an arginine to cysteine transition at position 141, R141C, which corresponds to mutation R142C in mouse NOTCH 3. CADASIL R142C mice show no apparent CADASIL‐like phenotype after histological and MRI analysis. The NOTCH 3 R142C receptor is processed normally and does not appear to accumulate the ectodomain, which has been observed in CADASIL patients. We discuss possible reasons for the different outcomes of the same germline CADASIL mutation in mice and humans. genesis 41:13–22, 2005. © 2005 Wiley‐Liss, Inc.