{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:13:55Z","timestamp":1792671235105,"version":"4.5.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008794","name":"Research Manitoba","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008794","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Sciences and Engineering Council of Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The GM2 gangliosidoses are lysosomal storage disorders exhibiting a spectrum of neurological phenotypes ranging from childhood death to debilitating adult-onset neurological impairment. To date, no mouse model harbouring a specific human mutation causing GM2 gangliosidosis has been created. We used CRISPR\/Cas9 to generate knockin (KI) mice with the common adult-onset Hexa Gly269Ser variant as well as knockout (KO) mice with Hexa mutations expected to cause complete HexA deficiency. We also created Neu3 KO alleles that combined with Hexa KO or KI alleles were expected to create acute and chronic models of GM2 gangliosidosis, respectively. However, both models accumulated GM2 ganglioside throughout the brain when compared to controls (CON), and exhibited progressive loss of reflexes, gait abnormalities, and premature death by 24\u2005weeks of age. Although survival and behavioural phenotypes did not differ between KO and KI models, the KI model had substantial Hexa mRNA and evidence of GM2 turnover. This KI model will be useful for developing gene editing to correct the variant causing the Gly269Ser substitution and its novel biochemical phenotype suggests it may be suitable for testing therapies that treat partial \u03b2-hexosaminidase A deficiency.<\/jats:p>","DOI":"10.1242\/bio.062045","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T07:42:11Z","timestamp":1757317331000},"source":"Crossref","is-referenced-by-count":4,"title":["Generation of mice with combined\n                    <i>Hexa<\/i>\n                    Gly269Ser KI or KO and\n                    <i>Neu3<\/i>\n                    KO alleles to create new models of GM2 gangliosidoses"],"prefix":"10.1242","volume":"14","author":[{"given":"Emily N.","family":"Barker","sequence":"first","affiliation":[{"name":"University of Manitoba 1 Department of Biochemistry and Medical Genetics , , Winnipeg , R3T 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