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?

Item Type:	Article
Title:	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?
Creators Name:	Puk, O. and Esposito, I. and Soeker, T. and Loester, J. and Budde, B. and Nuernberg, P. and Michel-Soewarto, D. and Fuchs, H. and Wolf, E. and Hrabe de Angelis, M. and Graw, J.
Abstract:	PURPOSE: The purpose of the present study was to characterize a new slit-eye phenotype in the mouse. METHODS: Genomewide linkage analysis was performed, and a candidate gene was sequenced. Eyes of the mutants were described morphologically, histologically, and by in situ hybridization. To allow morphologic and functional studies of the retina, mutants were outcrossed to C57BL/6. RESULTS: Within an ongoing ethyl-nitrosourea mutagenesis screen with C3HeB/FeJ mice, the authors 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. This mutation was mapped to the distal end of mouse chromosome 13, suggesting Fgf10 (encoding the fibroblast growth factor 10) as a candidate gene. 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 frameshift with a premature stop codon after 54 new amino acids was identified. Histologic analysis of the major ocular tissues (cornea, lens, retina) did not reveal major alterations compared with the wild type, but the size of the Harderian gland was remarkably reduced in heterozygotes. Although Fgf10 was expressed in the developing retina, neither electroretinography nor the virtual drum indicated any abnormalities in heterozygous mutants; overall eye size was identical in wild types and heterozygotes. CONCLUSIONS: The mutation in the Fgf10 gene leads to a dominant slit-eye phenotype caused by atrophy of the Harderian gland.
Keywords:	Amino Acid Sequence, Atrophy, Base Sequence, Mammalian Chromosomes, Animal Disease Models, Dry Eye Syndromes, Ethylnitrosourea, Eye Abnormalities, Fibroblast Growth Factor 10, Genome-Wide Association Study, Harderian Gland, Heterozygote, In Situ Hybridization, Crystalline Lens, Molecular Sequence Data, Mutation, Phenotype, Polymerase Chain Reaction, Retina, Animals, Mice
Source:	Investigative Ophthalmology & Visual Science
ISSN:	0146-0404
Publisher:	Association for Research in Vision and Ophthalmology
Volume:	50
Number:	9
Page Range:	4311-4318
Date:	September 2009
Official Publication:	https://doi.org/10.1167/iovs.09-3451
PubMed:	View item in PubMed

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