title: Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern.
abstract: The homozygous mouse mutant aphakia (ak) has been characterized by bilaterally aphakic eyes without a pupil [Varnum DS, Stevens, LC (1968): J Hered 59:147-150]. The mutation was mapped to chromosome 19 [Varnum DS, Stevens, LC (1975): Mouse News Lett 53:35]. Our linkage studies yielded a precise localization of the ak gene 0.6 +/- 0.3 cM proximal to the microsatellite marker D19Mit10 and 0.7 +/- 0.4 cM distal to D19Mit4 and D19Mit91. No recombination was found with the marker D19Mit9 among 418 backcross offspring tested. The developmental control gene Pax2 mapped 11.0 +/- 3.5 cM proximal to ak and is excluded as a candidate gene. Sequence analysis of Fgf8 and Chuk1, which are localized close to the marker D19Mit10, detected no mutations in the ak/ak mutants. Histological analysis of homozygous mutants suggested the arrest of lens development at the lens stalk stage, a transient morphological structure during the formation of the lens vesicle. In the lens remnants, Pax6 and Six3 are expressed, whereas in the persisting lens stalk only Pax6 was detected. The expression pattern of Pax2 appeared normal; Cryaa expression could not be detected. As a consequence of the arrested lens development, other ocular tissues that require for their development information from the intact lens, such as iris, ciliary muscle, retina, and vitreous body, are absent or formed abnormally.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Neuherberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Grimm
authors.forename: B
authors.initials: B
authors.lastname: Chatterjee
authors.forename: J
authors.initials: J
authors.lastname: Favor
authors.forename: T
authors.initials: T
authors.lastname: Immervoll
authors.forename: J
authors.initials: J
authors.lastname: Löster
authors.forename: N
authors.initials: N
authors.lastname: Klopp
authors.forename: R
authors.initials: R
authors.lastname: Sandulache
authors.forename: J
authors.initials: J
authors.lastname: Graw
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D005123:Eye / Q000196:embryology*; D005136:Eye Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D000097607:Homeobox Protein SIX3
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D000097607:Homeobox Protein SIX3; C000605732:Pax6 protein, mouse