RETINAL DYSPLASIA IN MICE LACKING P56(LCK)

The product of the proto-oncogene p56(lck) is a nonreceptor tyrosine k inase member of the Src family. It is found in T cells (Marth ef al,, 1985, 1988) and in the mouse brain (Omri et al., 1996; Van Tan et al., 1996). In this report, we describe experiments showing that Lck is pr esent in the mouse retina neurons. Lck gene expression was identified after isolating and sequencing the specific 5' and 3' part of the cDNA obtained by RT-PCR. In adult retina Lck immunoreactivity was most abu ndant in photoreceptor cells and within the outer plexiform layers. St aining was also observed in the inner nuclear and plexiform layers. In transgenic mice, the disruption of the Lck gene had serious consequen ces on the organization of the retina causing retinal dysplasia. These mice have partial retinal detachment with infolding and rosette forma tion in the photoreceptor sheet. These retinal abnormalities observed in Lck deficient mice lead to the loss of normal architecture of the p hotoreceptor and the inner nuclear layers, and provide an important ro le of Lck protein in the retina development. The lack of the Lck prote in produces a spectrum of retinal pathology that resembles human retin opathy of prematurity (ROP).