Generation of mice with a conditional null Fraser syndrome 1 (Fras1) allele.

Abstract

Fraser syndrome (FS) is an autosomal recessive disease characterized by skin lesions and kidney and upper airway malformations. Fraser syndrome 1 (FRAS1) is an extracellular matrix protein, and FRAS1 homozygous mutations occur in some FS individuals. FRAS1 is expressed at the epithelial-mesenchymal interface in embryonic skin and kidney. blebbed mice have a null Fras1 mutation and phenocopy human FS. Like humans with FS, they exhibit a high fetal and neonatal mortality, precluding studies of FRAS1 functions in later life. We generated conditional Fras1 null allele mice. Cre-mediated generalized deletion of this allele generated embryonic skin blisters and renal agenesis characteristic of blebbed mice and human FS. Targeted deletion of Fras1 in kidney podocytes circumvented skin blistering, renal agenesis, and early death. FRAS1 expression was downregulated in maturing glomeruli which then became sclerotic. The data are consistent with the hypothesis that locally produced FRAS1 has roles in glomerular maturation and integrity. This conditional allele will facilitate study of possible role for FRAS1 in other tissues such as the skin.

• Authors: Jolanta E Pitera, Mark Turmaine, Adrian S Woolf, Peter J Scambler
• Journal: Genesis (New York, N.Y. : 2000) (Genesis) Vol. 50 Issue 12 Pg. 892-8 (Dec 2012) ISSN: 1526-968X [Electronic] United States
• PMID: 22730198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Extracellular Matrix Proteins
• Fras1 protein, mouse

Topics

• Alleles
• Animals
• Blister (genetics, pathology)
• Congenital Abnormalities (genetics, pathology)
• Down-Regulation
• Extracellular Matrix Proteins (genetics, metabolism)
• Gene Deletion
• Kidney (abnormalities, pathology)
• Kidney Diseases (congenital, genetics, pathology)
• Mice
• Mice, Inbred C57BL
• Podocytes (pathology)