{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:20:56Z","timestamp":1788016856500,"version":"build-2784847793"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Constitutively active mutants of BRAF cause cardio-facio-cutaneous (CFC) syndrome, characterized by growth and developmental defects, cardiac malformations, facial features, cutaneous manifestations, and mental retardation. An animal model of human CFC syndrome, the systemic BrafQ241R\/+ mutant mouse, has been reported to exhibit multiple CFC syndrome-like phenotypes. In this study, we analyzed the effects of Braf mutations on neural function, separately from their effects on developmental processes. To this end, we generated Braf mutant mice expressing BRAFQ241R specifically in mature excitatory neurons (n-BrafQ241R\/+). We found no growth retardation or cardiac malformations in n-BrafQ241R\/+ mice, indicating normal development. Behavioral analysis revealed that n-BrafQ241R\/+ mice exhibited reduced home cage activity and learning disability, which were similar to those of systemic BrafQ241R\/+ mice. The active form of ERK was increased in the hippocampus of n-BrafQ241R\/+ mice, whereas basal synaptic transmission and synaptic plasticity in hippocampal Schaffer collateral-CA1 synapses seems to be normal. Transcriptome analysis of the hippocampal tissue revealed significant changes in the expression of genes involved in regulation of the RAS\/mitogen-activated protein kinase (MAPK) signaling pathway, synaptic function and memory formation. These data suggest that the neuronal dysfunction observed in the systemic CFC mouse model is due to the disruption of homeostasis of the RAS\/MAPK signaling pathway by the activated Braf mutant after maturation, rather than abnormal development of the brain. A similar mechanism may be possible in human CFC syndrome.<\/jats:p>","DOI":"10.1093\/hmg\/ddae196","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:01:23Z","timestamp":1736294483000},"page":"418-434","source":"Crossref","is-referenced-by-count":1,"title":["Q241R mutation of <i>Braf<\/i> causes neurological abnormalities in a mouse model of cardio-facio-cutaneous syndrome, independent of developmental malformations"],"prefix":"10.1093","volume":"34","author":[{"given":"Akira","family":"Moriya","sequence":"first","affiliation":[{"name":"Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences , 3-39-22 Showa-machi, Maebashi, Gunma 371-8514 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihito","family":"Saitow","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medicine, Nippon Medical School , 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moe","family":"Keitoku","sequence":"additional","affiliation":[{"name":"School of Science and Technology, Gunma University , 1-5-1 Tenjin-chou, Kiryu, Gunma 376-8515 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noato","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences , 3-39-22 Showa-machi, Maebashi, Gunma 371-8514 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsumi","family":"Oike","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences , 3-39-22 Showa-machi, Maebashi, Gunma 371-8514 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences , 3-39-22 Showa-machi, Maebashi, Gunma 371-8514 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiko","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences , 3-39-22 Showa-machi, Maebashi, Gunma 371-8514 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