Targeted Disruption of FSCN2 Gene Induces Retinopathy in Mice

Abstract

Abstract: : Purpose:To investigate morphology and function of photoreceptor in mice which have mutation of FSCN2gene. Methods:We have generated one mouse line carrying the 208delG mutation (point mutation type = p–type), and another with replacement of exon 1 by the cDNA of a green fluorescent protein (GFP knock–in type = g–type). Expression of retinal mRNA was determined by Reverse Transcription (RT) – Polymerase Chain Reaction (PCR) and in situ hybridization in retinal section. Morphological analyses of mouse retina were performed by Light Microscopy (LM) and Transmission Electron Microscopy (TEM). Functional analyses of mouse retina were performed by electroretinogram (ERG). Results:There was no FSCN2 mRNA from retinal mRNA extracted from FSCN2^p/p and FSCN2^g/g. Both FSCN2^+/p and FSCN2^+/g mice had progressive photoreceptor degeneration with increasing age by light microscopy. Transmission electron microscopic examination of both FSCN2^p/p and FSCN2^g/g mice demonstrated structural abnormalities of the Outer Segment (OS). Both FSCN2^+/p and FSCN2^+/g mice had depressed rod and cone electroretinographic responses that worsened with increasing age. Conclusions:These results indicated that haplo–insufficiency of the FSCN2 gene hampered the morphogenesis of the OS disks and resulted in photoreceptor degeneration at least as in human Autosomal Dominant Retinitis Pigmentosa (ADRP).

Keywords: retinal degenerations: cell biology • mutations • retina: distal (photoreceptors, horizontal cells, bipolar cells)