We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs.
- Authors
Jadeja, Shalini; Smyth, Ian; Pitera, Jolanta E; Taylor, Martin S; van Haelst, Mieke; Bentley, Elizabeth; McGregor, Lesley; Hopkins, Jason; Chalepakis, Georges; Philip, Nicole; Perez Aytes, Antonio; Watt, Fiona M; Darling, Susan M; Jackson, Ian; Woolf, Adrian S; Scambler, Peter J
- Abstract
Fraser syndrome is a recessive, multisystem disorder presenting with cryptophthalmos, syndactyly and renal defects and associated with loss-of-function mutations of the extracellular matrix protein FRAS1. Fras1 mutant mice have a blebbed phenotype characterized by intrauterine epithelial fragility generating serous and, later, hemorrhagic blisters. The myelencephalic blebs (my) strain has a similar phenotype. We mapped my to Frem2, a gene related to Fras1 and Frem1, and showed that a Frem2 gene-trap mutation was allelic to my. Expression of Frem2 in adult kidneys correlated with cyst formation in my homozygotes, indicating that the gene is required for maintaining the differentiated state of renal epithelia. Two individuals with Fraser syndrome were homozygous with respect to the same missense mutation of FREM2, confirming genetic heterogeneity. This is the only missense mutation reported in any blebbing mutant or individual with Fraser syndrome, suggesting that calcium binding in the CALXß-cadherin motif is important for normal functioning of FREM2.
- Subjects
GENES; GENETIC mutation; MICE; KIDNEY diseases; NOTORYCTEMORPHIA; EXTRACELLULAR matrix proteins
- Publication
Nature Genetics, 2005, Vol 37, Issue 5, p520
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1549