The high sensitivity of night vision requires that rod photoreceptors reliably and reproducibly signal the absorption of single photons, a process that depends upon tight regulation of intracellular cGMP concentration through the phototransduction cascade. Here in the mouse ( Mus musculus ), we studied a single-site D167A mutation of the gene for the alpha subunit of rod photoreceptor phosphodiesterase ( PDEA ), made with the aim of removing a noncatalytic binding site for cGMP. This mutation unexpectedly eliminated nearly all PDEA expression and reduced expression of the beta subunit gene ( PDEB ) to about 5 – 10% of wild-type (WT). The remaining phosphodiesterase had nearly normal specific activity; degeneration was slow, with 50–60% of rods remaining after 6 months. Responses were larger and more sensitive than normal but slower in rise and decay, probably from slower dark turnover of cGMP. Remarkably, responses became much less reproducible than WT, with response variance increasing for amplitude by ov...