Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems

David J. Pennisi, Lorine Wilkinson, Gabriel Kolle, Michael L. Sohaskey, Kevin Gillinder, Michael J. Piper, John W. McAvoy, Frank J. Lovicu, Melissa H Little

Research output: Contribution to journalArticleResearchpeer-review

48 Citations (Scopus)

Abstract

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. Crim1KST264/KST264 mice displayed perinatal lethality, syndactyly, eye, and kidney abnormalities. The severe and complex phenotype observed in Crim1KST264/KST264 mice highlights the importance of Crim1 in numerous aspects of organogenesis.

Original languageEnglish
Pages (from-to)502-511
Number of pages10
JournalDevelopmental Dynamics
Volume236
Issue number2
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

Keywords

  • Crim1
  • Gene-trap
  • Microphthalmia
  • Organogenesis
  • Skin blebbing
  • Syndactyly

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