Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice.

Abstract	Williams syndrome is a neurodevelopmental disorder caused by the hemizygous deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP-170 (a closely related cytoplasmic linker protein) and dynactin at the tips of growing microtubules. This protein redistribution may affect dynein motor regulation and, together with the loss of CLIP-115-specific functions, underlie neurological alterations in Williams syndrome.
Authors	Casper C Hoogenraad, Bas Koekkoek, Anna Akhmanova, Harm Krugers, Bjorn Dortland, Marja Miedema, Arjan van Alphen, Werner M Kistler, Martine Jaegle, Manoussos Koutsourakis, Nadja Van Camp, Marleen Verhoye, Annemie van der Linden, Irina Kaverina, Frank Grosveld, Chris I De Zeeuw, Niels Galjart
Journal	Nature genetics (Nat Genet) Vol. 32 Issue 1 Pg. 116-27 (Sep 2002) ISSN: 1061-4036 [Print] United States
PMID	12195424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Dynactin Complex Microtubule-Associated Proteins Neoplasm Proteins Nerve Tissue Proteins cytoplasmic linker protein 115 cytoplasmic linker protein 170 Dyneins
Topics	Animals Brain (abnormalities) Dynactin Complex Dyneins (metabolism) Gene Targeting Heterozygote Mice Mice, Knockout Microtubule-Associated Proteins (deficiency, genetics, metabolism) Motor Activity Mutagenesis, Site-Directed Neoplasm Proteins Nerve Tissue Proteins (deficiency, genetics) Phenotype Williams Syndrome (genetics, physiopathology)

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