{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:15:09Z","timestamp":1785467709570,"version":"3.56.0"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"The Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["23117713,16H06276 [AdAMS],18K06960,17H01391"],"award-info":[{"award-number":["23117713,16H06276 [AdAMS],18K06960,17H01391"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,19]]},"abstract":"<jats:p>\n                    Inosine triphosphate pyrophosphatase (ITPA) hydrolyzes inosine triphosphate (ITP) and other deaminated purine nucleotides to the corresponding nucleoside monophosphates. In humans, ITPA deficiency causes severe encephalopathy with epileptic seizure, microcephaly, and developmental retardation. In this study, we established neural stem cell\u2013specific\n                    <jats:italic>Itpa<\/jats:italic>\n                    \u2013conditional KO mice (\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice) to clarify the effects of ITPA deficiency on the neural system. The\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice showed growth retardation and died within 3 weeks of birth. We did not observe any microcephaly in the\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice, although the female\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice did show adrenal hypoplasia. The\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice showed limb-clasping upon tail suspension and spontaneous and\/or audiogenic seizure. Whole-cell patch-clamp recordings from entorhinal cortex neurons in brain slices revealed a depolarized resting membrane potential, increased firing, and frequent spontaneous miniature excitatory postsynaptic current and miniature inhibitory postsynaptic current in the\n                    <jats:italic>Itpa<\/jats:italic>\n                    -cKO mice compared with ITPA-proficient controls. Accumulated ITP or its metabolites, such as cyclic inosine monophosphates, or RNA containing inosines may cause membrane depolarization and hyperexcitability in neurons and induce the phenotype of ITPA-deficient mice, including seizure.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.140229","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T11:02:14Z","timestamp":1605697334000},"source":"Crossref","is-referenced-by-count":12,"title":["Neural stem cell\u2013specific ITPA deficiency causes neural depolarization and epilepsy"],"prefix":"10.1172","volume":"5","author":[{"given":"Yuichiro","family":"Koga","sequence":"first","affiliation":[{"name":"Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, 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