{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:52:10Z","timestamp":1777686730418,"version":"3.51.4"},"reference-count":68,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The Huntingtin (HTT) N-terminal domains encoded by Huntingtin\u2019 s ( HTT) exon 1 consist of an N17 domain, the polyglutamine (polyQ) stretch and a proline-rich region (PRR). These domains are conserved in mammals and have been hypothesized to modulate HTT\u2019s functions in the developing and adult CNS, including DNA damage repair and autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study longitudinally characterizes the in vivo consequences of deleting the murine Htt N-terminal domains encoded by Htt exon 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Knock-in mice with a deletion of Htt exon 1 sequences ( Htt\n                      <jats:sup>\u0394E1<\/jats:sup>\n                      ) were generated and bred into the C57BL\/6J congenic genetic background. Their behavior, DNA damage response, basal autophagy, and glutamatergic synapse numbers were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Progeny from Htt\n                      <jats:sup>\u0394E1\/+<\/jats:sup>\n                      intercrosses are born at the expected Mendelian frequency but with a distorted male to female ratio in both the Htt\n                      <jats:sup>\u0394E1\/ \u0394E1<\/jats:sup>\n                      and Htt\n                      <jats:sup>+\/+<\/jats:sup>\n                      offspring. Htt\n                      <jats:sup>\u0394E1\/ \u0394E1<\/jats:sup>\n                      adults exhibit a modest deficit in accelerating rotarod performance, and an earlier increase in cortical and striatal DNA damage with elevated neuronal pan-nuclear 53bp1 levels compared to Htt\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice. However, a normal response to induced DNA damage, normal levels of basal autophagy markers, and no significant differences in corticocortical, corticostriatal, thalamocortical, or thalamostriatal synapses numbers were observed compared to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our results suggest that deletion of the Htt N-terminus encoded by the Htt exon 1 does not affect Htt\u2019s critical role during embryogenesis, but instead, may have a modest effect on certain motor tasks, basal levels of DNA damage in the brain, and Htt function in the testis.<\/jats:p>\n                  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