title: A deletion in a cis element of Foxe3 causes cataracts and microphthalmia in rct mice.
abstract: The Rinshoken cataract (rct) mutation, which causes congenital cataracts, is a recessive mutation found in SJL/J mice. All mutants present with opacity in the lens by 2 months of age. The rct locus was mapped to a 1.6-Mb region in Chr 4 that contains the Foxe3 gene. This gene is responsible for cataracts in humans and mice, and it plays a crucial role in the development of the lens. Furthermore, mutation of Foxe3 causes various ocular defects. We sequenced the genomic region of Foxe3, including the coding exons and UTRs; however, no mutations were discovered in these regions. Because there were no differences in Foxe3 sequences between the rct/rct and wild-type mice, we inferred that a mutation was located in the regulatory regions of the Foxe3 gene. To test this possibility, we sequenced a 5' noncoding region that is highly conserved among vertebrates and is predicted to be the major enhancer of Foxe3. This analysis revealed a deletion of 22-bp located approximately 3.2-kb upstream of the start codon of Foxe3 in rct mice. Moreover, we demonstrated by RT-PCR and in situ hybridization that the rct mutant has reduced expression of Foxe3 in the lens during development. We therefore suggest that cataracts in rct mice are caused by reduced Foxe3 expression in the lens and that this decreased expression is a result of a deletion in a cis-acting regulatory element.
authors: Department of Bioproduction, Tokyo University of Agriculture, Abashiri, Hokkaido, Japan.
authors: Kenta
authors: K
authors: Wada
authors: Yukiko Y
authors: YY
authors: Maeda
authors: Kei
authors: K
authors: Watanabe
authors: Tatsuya
authors: T
authors: Oshio
authors: Takuya
authors: T
authors: Ueda
authors: Gou
authors: G
authors: Takahashi
authors: Michinari
authors: M
authors: Yokohama
authors: Junichi
authors: J
authors: Saito
authors: Yuta
authors: Y
authors: Seki
authors: Sumiyo
authors: S
authors: Takahama
authors: Rie
authors: R
authors: Ishii
authors: Hiroshi
authors: H
authors: Shitara
authors: Cyoji
authors: C
authors: Taya
authors: Hiromichi
authors: H
authors: Yonekawa
authors: Yoshiaki
authors: Y
authors: Kikkawa
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D007908:Lens, Crystalline / Q000473:pathology*; D051379:Mice; D008850:Microphthalmos / Q000235:genetics*; D009154:Mutation; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion
chemical_list: D051858:Forkhead Transcription Factors; C498612:Foxe3 protein, mouse