| First Author | Chang B | Year | 2024 |
| Mgi Jnum | J:345803 | Mgi Id | MGI:7611661 |
| Citation | Chang B (2024) The Mfrp |
| abstractText | The spontaneous mutation rd6-2J was discovered in our ocular phenotypes screening program in November 2013 in a female of strain B6.129S4-Ccl7tm1Ifc/J that presented with small retinal white dots at 7 weeks of age (Figure 1A) that were absent in her male littermate, which had a normal retina (Figure 1B). Subsequent retinal function tests also confirmed that the female had abnormal electroretinogram responses, but the male had normal retinal function. We mated the mutant female with C57BL/6J and all F1 mice had normal retinas. Linkage crosses then showed this spontaneous mutation to be an autosomal recessive mutation that maps to Chromosome 9 in the same location as the rd6 mutation. We did a complementation test between this new mutant and rd6, and the result was positive. rd6 is a 4 bp deletion in Mfrp that causes skipping of exon 4 and early termination of the protein sequence. Genotyping of the new mutation line for the rd6 mutation was negative proving this a novel mutation in Mfrp. We named the new retinal degeneration Mfrprd6-2J and we developed a C57BL/6J (B6) congenic strain, B6.Cg-Mfrprd6-2J/Boc (JAX Stock No. 036970), by backcrossing the Mfrprd6-2J allele from B6.129S4-Ccl7tm1Ifc/J (Jax Stock No. 017638) onto C57BL/6J for 2 generations then sibling mating to homozygosity. Rod electroretinogram assessment of homozygotes at 4 weeks of age showed a very small a-wave and reduced B-wave (dark adapted responses) and cone electroretinogram assessment showed reduced b-wave to about half normal levels. Because this phenotype is so reliable at 4 weeks of age, ERG was used to select homozygotes for breeding. The retinal white dots and degeneration phenotypes are very similar in B6.Cg-Mfrprd6-2J/Boc (Figure 1 C ) compared with B6.C3Ga-Mfrprd6/J (Jax Stock No. 003684) at 9 weeks of age (Figure 1D). The white retinal dots or spots remain clearly visible until about 7 months, when clinical signs of retinal degeneration first become evident, and become less easily distinguishable as degeneration progresses. This mutant has been suggested as a model for the human flecked retinal disorder retinitis punctata albicans (RPA), which causes progressive visual loss similar to that characteristic of retinitis pigmentosa. Sequencing of the Mfrp cDNA from Mfrprd6-2J failed to reveal a mutation in the coding sequence. |
