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Although both A-T mutated (<jats:italic>Atm<\/jats:italic>)- and transformation related protein 53 (<jats:italic>Trp53<\/jats:italic>)-dependent mechanisms are thought to clear newly postmitotic neurons with chromosome abnormalities, we found a 38% increase in the prevalence of XY aneuploidy in the adult<jats:italic>Atm<\/jats:italic><jats:sup>-\/-<\/jats:sup>cerebral cortex and a dramatic 78% decrease in<jats:italic>Trp53<\/jats:italic><jats:sup>-\/-<\/jats:sup>mutant mice. A similar 43% decrease in adult XY aneuploidy was observed in DNA repair-deficient<jats:italic>Xrcc5<\/jats:italic><jats:sup>-\/-<\/jats:sup>mutants. Additional investigation found an elevated incidence of aneuploid embryonic neural progenitor cells (NPCs) in all three mutants, but elevated apoptosis, a likely fate of embryonic NPCs with severe chromosome abnormalities, was observed only in<jats:italic>Xrcc5<\/jats:italic><jats:sup>-\/-<\/jats:sup>mutants. These data lend increasing support to the hypothesis that hereditary mutations such as ATM-deficiency, which render abnormal cells resistant to developmental clearance, can lead to late-manifesting human neurological disorders.<\/jats:p>","DOI":"10.1523\/jneurosci.2263-04.2004","type":"journal-article","created":{"date-parts":[[2004,9,15]],"date-time":"2004-09-15T19:22:48Z","timestamp":1095276168000},"page":"8090-8096","source":"Crossref","is-referenced-by-count":53,"title":["Failed Clearance of Aneuploid Embryonic Neural Progenitor Cells Leads to Excess Aneuploidy in the<i>Atm<\/i>-Deficient But Not the<i>Trp53<\/i>-Deficient Adult Cerebral Cortex"],"prefix":"10.1523","volume":"24","author":[{"given":"Michael J.","family":"McConnell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhruv","family":"Kaushal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy H.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcy A.","family":"Kingsbury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stevens K.","family":"Rehen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Treuner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Helton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily G.","family":"Annas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerold","family":"Chun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrolee","family":"Barlow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2004,9,15]]},"reference":[{"key":"2023041303082983000_24.37.8090.1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.869001"},{"key":"2023041303082983000_24.37.8090.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5346"},{"key":"2023041303082983000_24.37.8090.3","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/12.7.702"},{"key":"2023041303082983000_24.37.8090.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80086-0"},{"key":"2023041303082983000_24.37.8090.5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1242\/dev.122.4.1165","volume":"122","year":"1996","journal-title":"Development"},{"key":"2023041303082983000_24.37.8090.6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/BF01531506","volume":"15","year":"1985","journal-title":"J Autism Dev Disord"},{"key":"2023041303082983000_24.37.8090.7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00380.x"},{"key":"2023041303082983000_24.37.8090.8","doi-asserted-by":"crossref","unstructured":"Chun J, Blaschke AJ (1997) Identification of neural programmed cell death through the detection of DNA fragmentation in situ and by PCR. 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