{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T22:28:31Z","timestamp":1775082511983,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["CIFMS, 2021\u2010I2M\u20101\u2010024"],"award-info":[{"award-number":["CIFMS, 2021\u2010I2M\u20101\u2010024"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003996","name":"Kunming Medical University","doi-asserted-by":"publisher","award":["202201AY070001\u2010007"],"award-info":[{"award-number":["202201AY070001\u2010007"]}],"id":[{"id":"10.13039\/501100003996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease marked by significant clinical and genetic heterogeneity, primarily caused by expanded CAG mutations in the\n                      <jats:italic>ATXN2<\/jats:italic>\n                      gene. The unstable expansion of CAG repeats disrupts the genetic stability of animal models, which is detrimental to disease research.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we established a mouse model in which CAG repeats do not undergo microsatellite instability (MSI) across generations. A humanized\n                      <jats:italic>ATXN2<\/jats:italic>\n                      cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL\/6J mice. A 23 CAG control mouse model was also generated to verify\n                      <jats:italic>ATXN2<\/jats:italic>\n                      integration and expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In our model, the number of CAG repeats remained stable during transmission, with no CAG repeat expansion observed in 64 parent\u2010to\u2010offspring transmissions. Compared with SCA2\u2010Q23 mice, SCA2\u2010Q73 mice exhibited progressive motor impairment, reduced Purkinje cell count and volume (indicative of cell atrophy), and muscle atrophy. These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients. RNA\u2010seq analysis of the gastrocnemius muscle in SCA2\u2010Q73 mice showed significant changes in muscle differentiation and development gene expression at 56\u2009weeks, with no significant differences at 16\u2009weeks compared to SCA2\u2010Q23 mice. The expression level of the Myf6 gene significantly changed in the muscles of aged mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long\u2010term neural stimulation leads to muscle atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70047","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T01:39:52Z","timestamp":1750815592000},"page":"1677-1687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Establishment of a humanized\n                    <scp>SCA2<\/scp>\n                    mouse model carrying a\n                    <scp>CAA<\/scp>\n                    disruption preventing\n         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