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Mutations in transcription factors often exhibit pleiotropic effects related to their complex expression patterns and multiple regulatory targets. One such mutation in the zinc finger homeobox 3 (ZFHX3) transcription factor, short circuit (Sci, Zfhx3Sci/+ ), is associated with significant circadian deficits in mice. However, given evidence of its retinal expression, we set out to establish the effects of the mutation on retinal function using molecular, cellular, behavioral and electrophysiological measures. Immunohistochemistry confirms the expression of ZFHX3 in multiple retinal cell types, including GABAergic amacrine cells and retinal ganglion cells including intrinsically photosensitive retinal ganglion cells (ipRGCs). Zfhx3Sci/+ mutants display reduced light responsiveness in locomotor activity and circadian entrainment, relatively normal electroretinogram and optomotor responses but exhibit an unexpected pupillary reflex phenotype with markedly increased sensitivity. Furthermore, multiple electrode array recordings of Zfhx3Sci/+ retina show an increased sensitivity of ipRGC light responses.

Original publication

DOI

10.1096/fj.202100563R

Type

Journal article

Journal

FASEB J

Publication Date

09/2021

Volume

35

Keywords

amacrine cell, light sensitivity, mutation, pleiotropy, pupillary reflex, Amacrine Cells, Animals, Circadian Rhythm, Homeodomain Proteins, Light, Locomotion, Male, Mice, Mice, Inbred C57BL, Photic Stimulation, Retina, Retinal Ganglion Cells, Vision, Ocular