{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:14:20Z","timestamp":1788308060827,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":243,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Diseases and Stroke","award":["R01 NS068933"],"award-info":[{"award-number":["R01 NS068933"]}]},{"name":"National Institute of Neurological Diseases and Stroke","award":["R37 NS054154"],"award-info":[{"award-number":["R37 NS054154"]}]},{"name":"National Institute of Neurological Diseases and Stroke","award":["K99 NS130151"],"award-info":[{"award-number":["K99 NS130151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hereditary ataxias are a heterogeneous group of neurodegenerative disorders characterized by impaired balance and coordination, often due to cerebellar dysfunction. Despite advances in identifying genetic causes, animal models remain essential for dissecting underlying mechanisms and testing therapeutic strategies. Here we describe a mouse model of spastic ataxia and myopathy caused by a missense mutation in Tuba4a (n.A626C, p.Gln176Pro). In an ENU mutagenesis screen, a male C57BL\/6\u00a0J mouse exhibiting muscle wasting and an intention tremor starting at approximately 4\u00a0weeks-of-age was identified. The male was bred by in vitro fertilization to BALB\/cByJ oocyte donors. Genetic mapping determined dominant inheritance and localized the mutation to Chromosome 1. Genome sequencing revealed single nucleotide polymorphisms (SNPs) in serine threonine kinase 36 (Stk36Y1003N) and alpha-tubulin 4A (Tuba4aQ176P) in the mapping interval. These SNPs were CRISPR-engineered into C57BL\/6\u00a0J mice, which confirmed the Tuba4aQ176P variant as the causative mutation. Mutant mice are normal at 3\u00a0weeks, except for decrement in muscle response following repetitive nerve stimulation. However, by 30\u00a0days these mice have overt ataxia, Purkinje neuron degeneration, and extensive skeletal muscle defects, which contribute to a decreased lifespan. Dominant TUBA4A mutations in humans are associated with spastic ataxia type 11 (SPAX11), congenital myopathy type 26 (CMYO26), and frontotemporal dementia\/amyotrophic lateral sclerosis type 9 (FTDALS9). Our mice exhibit hallmark features of SPAX11 and CMYO26, but do not show motor neuron degeneration. This specificity makes this model a valuable tool for studying cell-type selective effects of TUBA4A mutations in neurodegeneration and myopathy.<\/jats:p>","DOI":"10.1093\/hmg\/ddag084","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:41:37Z","timestamp":1787658097000},"source":"Crossref","is-referenced-by-count":0,"title":["A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in\n                    <i>Tuba4a<\/i>"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0594-7354","authenticated-orcid":false,"given":"Timothy J","family":"Hines","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics , 600 Main Street, Bar Harbor, ME 04609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R","family":"Funke","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics , 600 Main Street, Bar Harbor, ME 04609 ,","place":["United States"]},{"name":"Neuroscience Ph.D. Program, Graduate School of Biomedical Science, 136 Harrison Ave, #813, Tufts University , Boston, MA 02111 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia L","family":"Pratt","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics , 600 Main Street, Bar Harbor, ME 04609 ,","place":["United States"]},{"name":"Neuroscience Ph.D. Program, Graduate School of Biomedical Science, 136 Harrison Ave, #813, Tufts University , Boston, MA 02111 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaura D","family":"Rice","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics , 600 Main Street, Bar Harbor, ME 04609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery L","family":"Twiss","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina , 700 Sumter St, #401, Columbia, SC 29208, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-3407","authenticated-orcid":false,"given":"Robert W","family":"Burgess","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Mammalian Genetics , 600 Main Street, Bar Harbor, ME 04609 ,","place":["United States"]},{"name":"Neuroscience Ph.D. Program, Graduate School of Biomedical Science, 136 Harrison Ave, #813, Tufts University , Boston, MA 02111 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2026090119312384400_ref1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E25-05-0247","article-title":"\u0391\u03b2-tubulin heterodimers: origins and regulation of 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