Abstract
Purpose :
To complete a clinical characterization and genetic analysis of a new mouse model bearing a spontaneous mutation named no b wave 10 (nob10).
Methods :
Retired mouse strains and stocks at The Jackson Laboratory for genetic mouse models of human ocular disorders using indirect ophthalmoscopy and ERG. We identified a new mouse model with a congenital no b wave phenotype. We characterized the clinical effects of this mutation in a longitudinal fashion using bright field retinal imaging with image-guided Optical Coherence Tomography (OCT), electroretinography (ERG) and histology. To identify the chromosomal location of the mutation, we performed genetic linkage analysis and tested candidate genes identified in the critical region.
Results :
Mice carrying the nob10 mutation show a congenital phenotype that can easily be recognized by ERG at three weeks of age with a no b wave rod-mediated photoresponse and an abnormal cone-mediated photoresponse. By fundus examination, mice homozygous for nob10 develop small, white dots throughout their retinas by 6 months of age. Histology and OCT at 6 months of age revealed a thinner retina with ~20-30% photoreceptor loss, with slow progressive loss thereafter. Genetic analysis showed that this disorder is caused by an autosomal recessive mutation that maps to mouse Chromosome 19, with close linkage to a microsatellite marker, D19Mit109. Examination of candidates within the region, revealed an excellent candidate gene, calcium binding protein 4 (Cabp4). However, there is no mutation found in the coding regions of the Cabp4 gene by sequence analysis.
Conclusions :
The nob10 is a new spontaneous mutation with no rod b wave and cone photoreceptor function loss. The phenotypes in the nob10 mice share similarities with that of congenital stationary night blindness, type 2b (CSNB2) patients and an important gene associated with CSNB2 is CABP4. Other human diseases associated with CABP4 are: cone-rod synaptic disorder (CRSD) and Leber congenital amaurosis (LCA). Genomic sequence analysis and expression analysis of Cabp4 are underway. Other candidates mapping within the critical region are Rom1 (rod outer segment membrane protein 1) and Best1 (bestrophin 1). The nob10 will provide a novel mouse model for study of human retinal diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.