Retinal degeneration in cone photoreceptor cell-ablatedtransgenic mice

[摘要] Purpose: To examine the effect of loss of cone photoreceptor cellson retinal degeneration.Methods: We previously identified a cone photoreceptor cell-specificpromoter of human cone transducin a-subunit (GNAT2) gene. In thisreport, a minigene, Trc-Tox176, that contains the GNAT2 promoter, anattenuated diphtheria toxin A-chain gene, and an enhancer element fromhuman interphotoreceptor retinoid-binding protein (IRBP) was used togenerate coneless transgenic mice. Transgenic mice were identified byPCR and the copy number of the transgene was determined by Southernhybridization, and examined by histology.Results: The results of immunostaining with anti-mouse GNAT2antibodies and reverse transcription-PCR (RT-PCR) analysis with mRNAfrom the retinas of transgenic mice showed that cone photoreceptor cellswere ablated in one of four transgenic mouse lines. The ablation of conecells began at postnatal day 8, at the same time as the expression ofendogenous GNAT2. An age-related rod degeneration was also found in thiscone-ablated mouse line, beginning at postnatal day 9, proceeding fromthe central retina to the peripheral retina.Conclusions: Cone photoreceptor cells may play an important role inthe survival of rod photoreceptor cells during mouse retinadevelopment.

[学科分类] 生物化学/生物物理