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Zfhx3 modulates retinal sensitivity and circadian responses to light
Author(s) -
Hughes Steven,
Edwards Jessica K.,
Wilcox Ashleigh G.,
Pothecary Carina A.,
Barnard Alun R.,
Joynson Russell,
Joynson Greg,
Hankins Mark W.,
Peirson Stuart N.,
Banks Gareth,
Nolan Patrick M.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100563r
Subject(s) - circadian rhythm , retina , intrinsically photosensitive retinal ganglion cells , retinal , medicine , erg , biology , endocrinology , transcription factor , microbiology and biotechnology , neuroscience , retinal ganglion cell , genetics , gene , biochemistry
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 , Zfhx3 Sci/+ ), 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). Zfhx3 Sci/+ 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 Zfhx3 Sci/+ retina show an increased sensitivity of ipRGC light responses.