title: Early transposable element insertion in intron 9 of the Hsf4 gene results in autosomal recessive cataracts in lop11 and ldis1 mice.
abstract: Lens opacity 11 (lop11) is an autosomal recessive mouse cataract mutation that arose spontaneously in the RIIIS/J strain. At 3 weeks of age mice exhibit total cataracts with vacuoles. The lop11 locus was mapped to mouse chromosome 8. Analysis of the mouse genome for the lop11 critical region identified Hsf4 as a candidate gene. Molecular evaluation of Hsf4 revealed an early transposable element (ETn) in intron 9 inserted 61 bp upstream of the intron/exon junction. The same mutation was also identified in a previously mapped cataract mutant, ldis1. The ETn insertion altered splicing and expression of the Hsf4 gene, resulting in the truncated Hsf4 protein. In humans, mutations in HSF4 have been associated with both autosomal dominant and recessive cataracts. The lop11 mouse is an excellent resource for evaluating the role of Hsf4 in transparency of the lens.
authors.affiliation: Department of Ophthalmology, Eye Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Elijah
authors.initials: E
authors.lastname: Talamas
authors.forename: Lavinia
authors.initials: L
authors.lastname: Jackson
authors.forename: Matthew
authors.initials: M
authors.lastname: Koeberl
authors.forename: Todd
authors.initials: T
authors.lastname: Jackson
authors.forename: John L
authors.initials: JL
authors.lastname: McElwee
authors.forename: Norman L
authors.initials: NL
authors.lastname: Hawes
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
authors.forename: D J
authors.initials: DJ
authors.lastname: Sidjanin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000503:physiopathology; D004251:DNA Transposable Elements / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics* / Q000502:physiology; D005808:Genes, Recessive; D000076249:Heat Shock Transcription Factors; D007438:Introns; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D000076249:Heat Shock Transcription Factors; C484462:Hsf4 protein, mouse; D014157:Transcription Factors