Selective Knockout of Murine Glutamic Acid-rich Protein 2 (GARP2) Significantly Alters Cellular Dark Noise in Rod Photoreceptors.

GARP2, a glutamic-acid-rich protein found exclusively in rod photoreceptors, has been suggested to function as a structural protein, a modulator of the cGMP phosphodiesterase enzyme (PDE6), and a gating inhibitor of the rod cGMP-gated cation channel. GARP2 is a splice variant of the Key Points: Glutamic acid-rich protein 2 (GARP2), an alternatively spliced variant of the Cngb1 gene, is exclusively expressed in rod photoreceptors, but the in vivo role of GARP2 remains unestablished.We used precision gene editing technology to selectively knockout soluble GARP2 expression in rods, to determine its essential functions in structure and function of the retina.We show that GARP2 has a minor role in maintaining the structural integrity of the rod outer segments as a function of age.Our study indicates that GARP2 has an important role in regulating rod photoreceptor dark noise, likely through stabilization of PDE6 basal activity to maintain the appropriate cGMP turnover rate.This regulation is critical to facilitate the single-photon sensitivity and function of the rod photoreceptors.