{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:55:24Z","timestamp":1787504124352,"version":"build-2736575974"},"posted":{"date-parts":[[2026,1,16]]},"group-title":"Neuroscience","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01EY033391"],"award-info":[{"award-number":["R01EY033391"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01EY033141"],"award-info":[{"award-number":["R01EY033141"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Angelina CASK Neurological Research Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Variants in the X-linked gene\n                  <jats:italic>CASK<\/jats:italic>\n                  are associated with neurodevelopmental defects. Animal model studies have demonstrated that conditions such as cerebellar hypoplasia, microcephaly, and optic nerve hypoplasia (ONH) are related to loss-of-function (LOF) in the\n                  <jats:italic>CASK<\/jats:italic>\n                  gene.\n                  <jats:italic>CASK<\/jats:italic>\n                  variants are associated with multiple ocular conditions spanning both anterior and posterior segments of the eye including retinopathies. Both\n                  <jats:italic>Cask<\/jats:italic>\n                  heterozygous knockout (+\/\u2212) mice and\n                  <jats:italic>Cask<\/jats:italic>\n                  knock-in (KI) mice with reduced\n                  <jats:italic>Cask<\/jats:italic>\n                  expression have been shown to display ONH.\n                  <jats:italic>Cask<\/jats:italic>\n                  (+\/\u2212) mice displayed no defects in retinal structure or function. Here, we have systematically examined the\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice. Our results demonstrate that the anterior segment of the eye in\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice does not display any obvious phenotype.\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice however show a reduced visual acuity in optomotor response. The retina of\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice does not exhibit any major changes in their structure, vasculature, or gene expression pattern. We, however, uncovered a specific dysfunction of the cone receptor in\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice using electroretinogram (ERG). Mechanistically this dysfunction arises due to lowered levels of cone-specific opsin (opsin1mw) in\n                  <jats:italic>Cask<\/jats:italic>\n                  (KI) mice. To the best of our knowledge, this is the first description of retinal dysfunction in an animal model with\n                  <jats:italic>CASK<\/jats:italic>\n                  gene suppression. We infer that like ONH and cerebellar hypoplasia, retinopathy also may represent\n                  <jats:italic>CASK<\/jats:italic>\n                  LOF.\n                <\/jats:p>","DOI":"10.64898\/2026.01.13.698659","type":"posted-content","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:00:12Z","timestamp":1768586412000},"source":"Crossref","is-referenced-by-count":1,"title":["CASK hypomorph mice display cone photoreceptor dysfunction"],"prefix":"10.64898","author":[{"given":"Sheida","family":"Hashemi","sequence":"first","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Y.","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushi","family":"Talajia","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Fortenberry","sequence":"additional","affiliation":[{"name":"Comprehensive Neuroscience Center, University of Alabama at Birmingham, AL 35233, USA"},{"name":"Vision Science Research Center, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Tufail","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice","family":"Turner","sequence":"additional","affiliation":[{"name":"School of Optometry, University of Alabama at Birmingham, AL 35233, USA"},{"name":"Comprehensive Neuroscience Center, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konark","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, AL 35233, USA"},{"name":"Vision Science Research Center, University of Alabama at Birmingham, AL 35233, USA"},{"name":"Comprehensive Neuroscience Center, University of Alabama at Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020607293074000_2026.01.13.698659v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.194"},{"issue":"12","key":"2026020607293074000_2026.01.13.698659v1.2","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/ajmg.a.35640","article-title":"Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations","volume":"158A","year":"2012","journal-title":"Am J Med Genet A"},{"key":"2026020607293074000_2026.01.13.698659v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02488.1996"},{"key":"2026020607293074000_2026.01.13.698659v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81736-5"},{"key":"2026020607293074000_2026.01.13.698659v1.5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.1.129"},{"key":"2026020607293074000_2026.01.13.698659v1.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109806200"},{"key":"2026020607293074000_2026.01.13.698659v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/35005118"},{"key":"2026020607293074000_2026.01.13.698659v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2183-4"},{"key":"2026020607293074000_2026.01.13.698659v1.9","doi-asserted-by":"crossref","unstructured":"Mukherjee K , Sharma M , Jahn R , Wahl MC , Sudhof TC . 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Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). Plos One. 2017;12(8).","DOI":"10.1371\/journal.pone.0181791"},{"key":"2026020607293074000_2026.01.13.698659v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.220"},{"key":"2026020607293074000_2026.01.13.698659v1.18","unstructured":"Moog U , Uyanik G , Kutsche K. CASK-Related Disorders. In: Adam MP , Ardinger HH , Pagon RA , Wallace SE , Bean LJH , Stephens K , et al., editors. GeneReviews((R)). 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Gene Therapy for Achromatopsia. 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