Mice carrying a R142C Notch 3 knock–in mutation do not develop a CADASIL-like phenotype

✍ Scribed by Johan Lundkvist; Shunwei Zhu; Emil M. Hansson; Petra Schweinhardt; Qing Miao; Paul Beatus; Karin Dannaeus; Helena Karlström; Clas B. Johansson; Matti Viitanen; Björn Rozell; Christian Spenger; Abdul Mohammed; Hannu Kalimo; Urban Lendahl

• Book ID: 102223843
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 410 KB
• Volume: 41
• Category: Article
• ISSN: 1526-954X
• DOI: 10.1002/gene.20091

✦ Synopsis

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 inframe 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.