Nature Genetics
34, 209 - 214 (2003)
Published online: 25 May 2003; | doi:10.1038/ng1168
Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in miceSophia Vrontou1, 2, Petros Petrou1, Barbara I Meyer3, Vassilis K Galanopoulos2, Kenji Imai4, Masayuki Yanagi4, Kamal Chowdhury3, Peter J Scambler5
& Georges Chalepakis1, 21
Institute of Molecular Biology and Biotechnology, FO.R.T.H., Heraklion 71110, Crete, Greece. 2
Department of Biology, University of Crete, Heraklion 71409, Crete, Greece. 3
Max-Planck-Institute of Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg 11, D-37077 Goettingen, Germany. 4
GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany. 5
Molecular Medicine, Unit, Institute of Child Health, London WC1N 1EH, UK.
Correspondence should be addressed to Georges Chalepakis chalepak@imbb.forth.grLoss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins1,
2. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants3,
4, which have been considered a model for the human genetic disorder Fraser syndrome5,
6. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice6. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.
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