A New Mouse Model for Complete Congenital Stationary Night Blindness Due to Gpr179 Deficiency

Mutations in GPR179 lead to autosomal recessive complete congenital stationary night blindness (cCSNB). This condition represents a signal transmission defect from the photoreceptors to the ON-bipolar cells. To confirm the phenotype, better understand the pathogenic mechanism in vivo, and provide a model for therapeutic approaches, a Gpr179 knock-out mouse model was genetically and functionally characterized. We confirmed that the insertion of a neo/lac Z cassette in intron 1 of Gpr179 disrupts the same gene. Spectral domain optical coherence tomography reveals no obvious retinal structure abnormalities. Gpr179 knock-out mice exhibit a so-called no-b-wave (nob) phenotype with severely reduced b-wave amplitudes in the electroretinogram. Optomotor tests reveal decreased optomotor responses under scotopic conditions. Consistent with the genetic disruption of Gpr179, GPR179 is absent at the dendritic tips of ON-bipolar cells. While proteins of the same signal transmission cascade (GRM6, LRIT3, and TRPM1) are correctly localized, other proteins (RGS7, RGS11, and GNB5) known to regulate GRM6 are absent at the dendritic tips of ON-bipolar cells. These results add a new model of cCSNB, which is important to better understand the role of GPR179, its implication in patients with cCSNB, and its use for the development of therapies.

Automated summary

Mutations in GPR179 gene cause autosomal recessive complete congenital stationary night blindness (cCSNB), and a Gpr179 knock-out mouse model has been used to understand the pathogenic mechanism and develop therapeutic approaches. The knock-out mice exhibit reduced b-wave amplitudes in electroretinogram and decreased optomotor responses, indicating a disruption in signal transmission from photoreceptors to ON-bipolar cells. This new model provides insights into the role of GPR179 in patients with cCSNB and its potential for therapeutic development.