{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:41Z","timestamp":1785435581913,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23K07284"],"award-info":[{"award-number":["23K07284"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP22H03049"],"award-info":[{"award-number":["JP22H03049"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP20K21589"],"award-info":[{"award-number":["JP20K21589"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015120","name":"Daiko Foundation","doi-asserted-by":"publisher","award":["9234"],"award-info":[{"award-number":["9234"]}],"id":[{"id":"10.13039\/100015120","id-type":"DOI","asserted-by":"publisher"}]},{"award":["9234"],"award-info":[{"award-number":["9234"]}],"id":[{"id":"https:\/\/ror.org\/02kjy3s76","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020236","name":"Japan Foundation for Pediatric Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020236","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Centrosomal protein 152 (CEP152) is a key regulator of centriole architecture and function, essential for proper cell division and polarity. Pathogenic variants in CEP152 cause Seckel syndrome (SCKL), a systemic disorder characterized by microcephalic primordial dwarfism. However, the mechanisms underlying its multi-organ manifestations remain poorly understood. To investigate this, we utilized two mouse models harboring patient-derived CEP152 variants, Cep152W105*\/K897* and Cep152Q32P\/Q32P. While our previous work focused on neurodevelopmental defects, here we systematically analyzed extra-neuronal phenotypes. We identified impaired spermatogenesis, characterized by defective mitosis and increased apoptosis in spermatogonia, as well as hematological abnormalities indicative of macrocytic anemia. In addition, we found reduced expression of Opalin, a gene involved in oligodendrocyte differentiation, and decreased numbers of Olig2-positive oligodendrocytes, suggesting broader glial deficits beyond recently characterized neuronal abnormalities. Collectively, our results highlight the role of CEP152 dysfunction in multi-systemic abnormalities of SCKL and provide an integrative view of its impact on both neuronal and extra-neuronal development.<\/jats:p>","DOI":"10.3390\/cells15131148","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"1148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extra-Neurological Characterization of Seckel Syndrome-Model Mice Harboring CEP152 Variants"],"prefix":"10.3390","volume":"15","author":[{"given":"Nanako","family":"Hamada","sequence":"first","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5373-7471","authenticated-orcid":false,"given":"Koki","family":"Ichihashi","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Gifu University School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-2406","authenticated-orcid":false,"given":"Tohru","family":"Matsuki","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-0800","authenticated-orcid":false,"given":"Atsuo","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Gifu University School of Medicine, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-8434","authenticated-orcid":false,"given":"Koh-ichi","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Japan"},{"name":"Department of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"},{"name":"Hirano General Hospital, Gifu 501-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrm2180","article-title":"Centrosome Biogenesis and Function: Centrosomics Brings New Understanding","volume":"8","author":"Glover","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrm4062","article-title":"Centrosome Function and Assembly in Animal Cells","volume":"16","author":"Conduit","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1247\/csf.20007","article-title":"Centrosomal and Non-Centrosomal Functions Emerged through Eliminating Centrosomes","volume":"45","author":"Takeda","year":"2020","journal-title":"Cell Struct. Funct."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature08136","article-title":"A Mechanism Linking Extra Centrosomes to Chromosomal Instability","volume":"460","author":"Ganem","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.cell.2008.05.039","article-title":"Centrosome Amplification Can Initiate Tumorigenesis in Flies","volume":"133","author":"Basto","year":"2008","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nrc924","article-title":"Centrosome Aberrations: Cause or Consequence of Cancer Progression?","volume":"2","author":"Nigg","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.tig.2011.05.004","article-title":"Centrosomes and Cilia in Human Disease","volume":"27","author":"Hildebrandt","year":"2011","journal-title":"Trends Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.gde.2012.04.006","article-title":"The Ciliopathies: A Transitional Model into Systems Biology of Human Genetic Disease","volume":"22","author":"Davis","year":"2012","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"W317","DOI":"10.1093\/nar\/gkp416","article-title":"GeneCodis: Interpreting Gene Lists through Enrichment Analysis and Integration of Diverse Biological Information","volume":"37","author":"Vazquez","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nature02166","article-title":"Proteomic Characterization of the Human Centrosome by Protein Correlation Profiling","volume":"426","author":"Andersen","year":"2003","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.cub.2007.09.031","article-title":"Asterless Is a Centriolar Protein Required for Centrosome Function and Embryo Development in Drosophila","volume":"17","author":"Varmark","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1534\/genetics.108.095141","article-title":"Drosophila Asterless and Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication","volume":"180","author":"Blachon","year":"2008","journal-title":"Genetics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nature09445","article-title":"Asterless Is a Scaffold for the Onset of Centriole Assembly","volume":"467","author":"Dzhindzhev","year":"2010","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1083\/jcb.201007107","article-title":"Cep152 Acts as a Scaffold for Recruitment of Plk4 and CPAP to the Centrosome","volume":"191","author":"Cizmecioglu","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20130460","DOI":"10.1098\/rstb.2013.0460","article-title":"The Centriole Duplication Cycle","volume":"369","author":"Stearns","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1042\/EBC20180036","article-title":"Bridging Centrioles and PCM in Proper Space and Time","volume":"62","author":"Varadarajan","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ng.725","article-title":"CEP152 Is a Genome Maintenance Protein Disrupted in Seckel Syndrome","volume":"43","author":"Kalay","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e07519","DOI":"10.7554\/eLife.07519","article-title":"Centriolar Satellites Assemble Centrosomal Microcephaly Proteins to Recruit CDK2 and Promote Centriole Duplication","volume":"4","author":"Kodani","year":"2015","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/ng.971","article-title":"A Primary Microcephaly Protein Complex Forms a Ring around Parental Centrioles","volume":"43","author":"Sir","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.cub.2014.01.067","article-title":"Proximity Interactions among Centrosome Components Identify Regulators of Centriole Duplication","volume":"24","author":"Rauniyar","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Brown, N.J., Marjanovi\u0107, M., L\u00fcders, J., Stracker, T.H., and Costanzo, V. (2013). Cep63 and Cep152 Cooperate to Ensure Centriole Duplication. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069986"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/nsmb.2846","article-title":"Molecular Basis for Unidirectional Scaffold Switching of Human Plk4 in Centriole Biogenesis","volume":"21","author":"Park","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_23","first-page":"3223","article-title":"Human Cep192 and Cep152 Cooperate in Plk4 Recruitment and Centriole Duplication","volume":"126","author":"Sonnen","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/(SICI)1096-8628(19970516)70:2<155::AID-AJMG10>3.0.CO;2-I","article-title":"Central Nervous System Anomalies in Seckel Syndrome: Report of a New Family and Review of the Literature","volume":"70","author":"Shanske","year":"1997","journal-title":"Am. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ng.2007.80","article-title":"Mutations in Pericentrin Cause Seckel Syndrome with Defective ATR-Dependent DNA Damage Signaling","volume":"40","author":"Griffith","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1038\/s44321-026-00427-3","article-title":"Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities","volume":"18","author":"Hamada","year":"2026","journal-title":"EMBO Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1538\/expanim.60.481","article-title":"Effect of Three Types of Mixed Anesthetic Agents Alternate to Ketamine in Mice","volume":"60","author":"Kawai","year":"2011","journal-title":"Exp. Anim."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/ng.420","article-title":"A Mouse Model of ATR-Seckel Shows Embryonic Replicative Stress and Accelerated Aging","volume":"41","author":"Murga","year":"2009","journal-title":"Nat. Genet."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:58:51Z","timestamp":1782536331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":28,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15131148"],"URL":"https:\/\/doi.org\/10.3390\/cells15131148","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}