Retinal degeneration in cone photoreceptor cell-ablated transgenic mice

PURPOSE: To examine the effect of loss of cone photoreceptor cells on retin al degeneration. METHODS: We previously identified a cone photoreceptor cell-specific promot er of human cone transducin alpha-subunit (GNAT2) gene. In this report, a m inigene, Trc-Tox176, that contains the GNAT2 promoter, an attenuated diphth eria toxin A-chain gene, and an enhancer element from human interphotorecep tor retinoid-binding protein (IRBP) was used to generate coneless transgeni c mice. Transgenic mice were identified by PCR and the copy number of the t ransgene was determined by Southern hybridization, and examined by histolog y. RESULTS: The results of immunostaining with anti-mouse GNAT2 antibodies and reverse transcription-PCR (RT-PCR) analysis with mRNA from the retinas of transgenic mice showed that cone photoreceptor cells were ablated in one of four transgenic mouse lines. The ablation of cone cells began at postnatal day 8, at the same time as the expression of endogenous GNAT2. An age-rela ted rod degeneration was also found in this cone-ablated mouse line, beginn ing at postnatal day 9, proceeding from the central retina to the periphera l retina. CONCLUSIONS: Cone photoreceptor cells may play an important role in the sur vival of rod photoreceptor cells during mouse retina development.