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

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. 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.

Renal organogenesis

“…3I). 45 Crim1 is also expressed in the mesangial cells (Fig. 3J), which are regarded as derivatives of the pericytic compartment and in the papilla (Fig.…”

“…They also show enriched expression of Crim1, a transmembrane regulator of growth factors that we have previously described within the kidney. 44,45 We have previously localized the expression of…”

“…We were characterizing the phenotype of a hypomorph of Crim1 to look for a role for the gene in kidney development. 45 This was long before we knew anything about renal MSCs. The Crim1 hypomorph has a very complex phenotype in the animal as a whole.…”

“…This is published work. 45 We see a disruption to VEGF signaling from the podocyes, such that you get a disruption to glomerular vascular development and glomerulur cysts. 44 You also get digital anomalies, lens defects as well as other defects.…”

“…44 You also get digital anomalies, lens defects as well as other defects. 45 We have really focused on what that gene is doing in terms of development and haven't challenged the mice to ask how they respond to repair. However, these mice do progress spontaneously to BMP, notch and Wnt families in that distal side.…”