title: Identification of a mutation in the MP19 gene, Lim2, in the cataractous mouse mutant To3.
abstract: OBJECTIVE
  Lim2, the gene encoding the second most abundant lens specific integral membrane protein, MP19, has recently been proposed as an ideal candidate gene for the cataractous mouse mutant, To3. The aim of this study was to screen the Lim2 gene in the To3 mutant for a genetic lesion that was correlated and consistent with the mutant phenotype.
  
  
  METHODS
  Genomic DNA was isolated from both normal mouse parental strains as well as the heterozygous and homozygous To3 cataract mutant. PCR was used to generate overlapping fragments of the entire Lim2 gene from these DNAs. The coding regions, including splice junctions and the translational termination site, of these fragments were then sequenced.
  
  
  RESULTS
  A single G -> T transversion was identified within the first coding exon of the Lim2 gene in the To3 mutant DNA. This DNA change results in the nonconservative substitution of a valine for the normally encoded glycine at amino acid 15 of the MP19 polypeptide.
  
  
  CONCLUSIONS
  The identified genetic lesion in the Lim2 gene of the cataractous mouse mutant, To3, confirms Lim2 as an ideal candidate gene. Future transgenic experiments should provide proof or disproof of a causative relationship between the identified mutation and the cataractous phenotype. These studies indicate that MP19 may play an important role in both normal lens development and cataractogenesis, and warrants more intense investigation of its role within the ocular lens.
authors.affiliation: Emory Eye Center, Emory University School of Medicine, Department of Ophthalmology, Atlanta, GA, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Steele
authors.forename: S
authors.initials: S
authors.lastname: Kerscher
authors.forename: M F
authors.initials: MF
authors.lastname: Lyon
authors.forename: P H
authors.initials: PH
authors.lastname: Glenister
authors.forename: J
authors.initials: J
authors.lastname: Favor
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R L
authors.initials: RL
authors.lastname: Church
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D003433:Crosses, Genetic; D005136:Eye Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary
chemical_list: D005136:Eye Proteins; C489025:Lim2 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins