The Dry Eye Zone

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Abstract: Fgf10 mutation, atrophy of the Harderian gland

Invest Ophthalmol Vis Sci. 2009 Apr 30. [Epub ahead of print]Links
A new Fgf10 mutation in the mouse leads to atrophy of the Harderian gland and slit-eye phenotype in heterozygotes: A novel model for dry-eye disease?

Puk O, Esposito I, Söker T, Löster J, Budde B, Nürnberg P, Michel-Soewarto D, Fuchs H, Wolf E, Hrabé de Angelis M, Graw J.
Helmholtz Center Munich, Neuherberg, Germany.

Purpose: Aim of the present study is the molecular and phenotypical characterization of a new slit-eye phenotype in the mouse.

Methods: Genome-wide linkage analysis was performed and a candidate gene has been sequenced. Eyes of the mutants were described morphologically, histologically, and by in-situ hybridization. To allow morphological and functional studies of the retina, mutants have been out-crossed to C57BL/6.

Results: Within an ongoing ENU mutagenesis screen with C3HeB/FeJ mice, we identified a new mutant (referred to as Aey17) showing a slit-eye phenotype in heterozygotes; homozygous mutants are not viable because of major developmental defects. We mapped this mutation to the distal end of mouse chromosome 13 suggesting Fgf10 (encoding the fibroblast growth factor 10) as a candidate gene. We identified an A-->G transition in the penultimate base of the first intron of Fgf10 leading to aberrant splicing with an additional 49 bp in exon 2 and to a frame shift with a premature stop codon after 54 new amino acids. The histological analysis of the major ocular tissues (cornea, lens, retina) did not reveal major alterations as compared to the wild type, but the size of the Harderian gland was remarkably reduced in heterozygotes. Although Fgf10 is expressed in the developing retina, neither eletroretinography nor the virtual drum indicated any abnormalities in heterozygous mutants; the overall eye size was identical in wild types and heterozygotes.

Conclusions: The mutation in the Fgf10 gene leads a dominant slit-eye phenotype caused by an atrophy of the Harderian gland.