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Crim1 KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems
Author(s) -
Pennisi David J.,
Wilkinson Lorine,
Kolle Gabriel,
Sohaskey Michael L.,
Gillinder Kevin,
Piper Michael J.,
McAvoy John W.,
Lovicu Frank J.,
Little Melissa H.
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21015
Subject(s) - biology , transgene , microbiology and biotechnology , phenotype , podocyte , kidney , gene , endocrinology , genetics , proteinuria
Crim1 is a transmembrane protein, containing six vWF‐C type cysteine‐rich repeats, that tethers growth factors to the cell surface. A mouse line, KST264, generated in a LacZ insertion mutagenesis gene‐trap screen, was examined to elucidate Crim1 function in development. We showed that Crim1 KST264/KST264 mice were not null for Crim1 due to the production of a shortened protein isoform. These mice are likely to represent an effective hypomorph or a dominant‐negative for Crim1. Transgene expression recapitulated known Crim1 expression in lens, brain, and limb, but also revealed expression in the smooth muscle cells of the developing heart and renal vasculature, developing cartilage, mature ovary and detrusor of the bladder. Transgene expression was also observed in glomerular epithelial cells, podocytes, mesangial cells, and urothelium in the kidney. Crim1 KST264/KST264 mice displayed perinatal lethality, syndactyly, eye, and kidney abnormalities. The severe and complex phenotype observed in Crim1 KST264/KST264 mice highlights the importance of Crim1 in numerous aspects of organogenesis. Developmental Dynamics 236:502–511, 2007. © 2006 Wiley‐Liss, Inc.