In this knockout strain, exon 6 of the semaphorin 5A (Sema5a) gene is excised (includes coding region), abolishing gene function. Sema5A is a transmembrane protein which acts as a repellant for axonal guidance during retinal neural development. Wildtype P0 and P3 mice express Sema5A in the outer neuroblastic layer, directly adjacent to the inner neuroblastic layer (INBL). At P7, P10, and P14, the expression is only observed in the middle to outer part of inner nuclear layer (INL), and transcripts are not detectable at P21, when retinal development is almost complete. Homozygotes are viable and fertile. When bred to mice lacking Sema5b (Stock No. 017534), SEMA5A/B double KO mice exhibit severe defects in retinal ganglion cells, amacrine cells, cholinergic amacrine cells, calretinin-positive amacrine cells, and calbindin-positive amacrine cells. The defects lead to neurite mistargeting within both the inner plexiform layer (IPL) and INL resulting in functional defects in retinal responses to visual stimuli. These mice may be useful for studying axonal guidance and lamination regulation during retinal development.
