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D.M. Maddox, N.L. Hawes, B. Chang, J.K. Naggert, P.M. Nishina; High Resolution Mapping of the Dice Mutation, a Genetic Defect Leading to Early–Onset Diminished Cone Electroretinogram Recordings, on Mouse Chromosome 12 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3277.
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© ARVO (1962-2015); The Authors (2016-present)
The dice mutation arose spontaneously on the B6.129S7–Ifingr1<tm1Agt> background. Mice homozygous for the dice mutation exhibit diminished cone electroretinogram (ERG) readings at three weeks of age. The purpose of this study was to determine the chromosomal location of the dice mutation and to identify the molecular lesion underlying the dice phenotype.
Mice homozygous for the dice mutation were mated to DBA/2J mice to produce F1 progeny. The F1 progeny were then intercrossed to produce 199 F2 mice that were phenotyped by electroretinography. The Fine Mapping Laboratory at The Jackson Laboratory pooled DNA samples from the first 15 dice F2 mutant mice and performed a genome scan against pooled DNA from phenotypically normal littermates. Strongest bias for B6 alleles was obtained on chromosome 12, for markers D12Mit190 (56.4 megabases or Mb) and D12Mit5 (77.7 Mb). Refinement of the map position was achieved by genotyping mice recombinant between these two markers with closely spaced simple sequence length polymorphism (SSLP) markers that mapped within the critical region on chromosome 12.
The dice mutation maps to a 2.9 Mb region on chromosome 12, between markers D12Mit286 (72.9 Mb) and D12Mit4 (75.8 Mb) based on 398 meioses from a B6.129S7–Ifngr1<tm1Agt>/J–dice X DBA/2J intercross. Contained within this region are 19 annotated and 7 novel genes.
The dice mutation causes a phenotype of early–onset cone dysfunction with variable rod involvement. As none of the genes within the dice critical region have been reported to be involved in cone development/function, it appears that the dice mutation is a novel model of attenuated cone ERG response. Identification of the precise genetic lesion underlying the dice mutant phenotype will allow for the development of a screen to identify potential genetic defects in human patients with cone ERG disorders who lack mutations in previously identified cone dystrophy genes.
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