EXPRESSION OF THE CNGB3 SUBUNIT IN RETINA OF ACHROMATOPSIA-AFFECTED DOGS

Abstract

Light energy is converted into an electrical signal by a set of proteins in the phototransduction cascade in photoreceptors. In this work, I focus on two critical elements of the phototransduction cascade in canine, the opsin molecules and CNG channels of cone photoreceptors. Canines are dichromats possessing two types of cone photoreceptors with different opsin molecules that detect either long and medium wavelengths (L/M) or short wavelengths (S). The L/M- and S-opsin genes were cloned from an Alaskan Malamute and used to investigate key amino acids that are responsible for tuning the spectral properties of the 11-cis retinal chromophore. Cone CNG channels are composed of CNGA3 and CNGB3 subunits. I characterized antibodies to detect cone CNG channel subunits to investigate expression of mutations in CNGB3 subunit on two canine models for achromatopsia. One model contains a missense CNGB3 mutation D262N (CNGB3m/m) and the other is a complete deletion of all exons of the CNGB3 gene (CNGB3-/-). Studies presented in this thesis show CNGB3 is expressed later in cone during retinal development compared to CNGA3. It also presents evidence for the necessity of CNGB3 in cone outer segment targeting of CNGA3.