{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:52:47Z","timestamp":1791233567269,"version":"4.1.0"},"reference-count":31,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"crossref","award":["ZIA HD008988"],"award-info":[{"award-number":["ZIA HD008988"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["1ZIAHG000068-15"],"award-info":[{"award-number":["1ZIAHG000068-15"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hide & Seek Foundation for Lysosomal Disease Research"},{"name":"Dana's Angels Research Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. However, clinical manifestations occurring in both patients and mammalian models offer significant translational value. Many neurological disorders, including inherited, metabolic Niemann\u2013Pick disease, type C (NPC), exhibit ataxia. Both individuals with NPC and murine models manifest ataxia, and investigational therapies impacting this phenotype in mice have been reported to slow disease progression in patients (e.g. miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, and acetyl-L-leucine). Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. Previously, other groups have developed a composite phenotypic scoring system (CPSS), which was subsequently used to distinguish strain-dependent phenotypes and, with modifications, to evaluate potential therapies. However, high inter-rater reliability is paramount to widespread use. We have created a comprehensive, easy-to-follow phenotypic assessment based on the CPSS and have verified its reproducibility using murine models of NPC disease. Application of this scoring system is not limited to NPC disease and may be applicable to other models of neurodegeneration exhibiting motor incoordination, thereby increasing its utility in translational studies.<\/jats:p>","DOI":"10.1242\/bio.059052","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T13:41:36Z","timestamp":1650634896000},"source":"Crossref","is-referenced-by-count":27,"title":["Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann\u2013Pick disease, type C1"],"prefix":"10.1242","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-4617","authenticated-orcid":false,"given":"Julia","family":"Yerger","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-7540","authenticated-orcid":false,"given":"Antony C.","family":"Cougnoux","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig B.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Luke","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2762-1766","authenticated-orcid":false,"given":"Tannia S.","family":"Clark","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, Genetic Disease Research Branch, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-5941","authenticated-orcid":false,"given":"Niamh X.","family":"Cawley","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0046","authenticated-orcid":false,"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-8113","authenticated-orcid":false,"given":"Cristin D.","family":"Davidson","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, Genetic Disease Research Branch, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"2022050310225812400_BIO059052C1","doi-asserted-by":"publisher","first-page":"326ra23","DOI":"10.1126\/scitranslmed.aad9407","article-title":"Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model","volume":"8","author":"Alam","year":"2016","journal-title":"Sci. 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