Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1
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–Pick disease,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2022-04-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/11/4/bio059052 |
| _version_ | 1818263412550926336 |
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| author | Julia Yerger Antony C. Cougnoux Craig B. Abbott Rachel Luke Tannia S. Clark Niamh X. Cawley Forbes D. Porter Cristin D. Davidson |
| author_facet | Julia Yerger Antony C. Cougnoux Craig B. Abbott Rachel Luke Tannia S. Clark Niamh X. Cawley Forbes D. Porter Cristin D. Davidson |
| author_sort | Julia Yerger |
| collection | DOAJ |
| description | 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–Pick 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. |
| first_indexed | 2024-12-12T19:18:36Z |
| format | Article |
| id | doaj.art-cc234da7a6fd42d490be17cdf8be41d1 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-12T19:18:36Z |
| publishDate | 2022-04-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-cc234da7a6fd42d490be17cdf8be41d12022-12-22T00:14:41ZengThe Company of BiologistsBiology Open2046-63902022-04-0111410.1242/bio.059052059052Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1Julia Yerger0Antony C. Cougnoux1Craig B. Abbott2Rachel Luke3Tannia S. Clark4Niamh X. Cawley5Forbes D. Porter6Cristin D. Davidson7 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA National Human Genome Research Institute, Genetic Disease Research Branch, NIH, Bethesda, MD 20892, USA Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Dysmorphology, NIH, Bethesda, MD, 20892, USA National Human Genome Research Institute, Genetic Disease Research Branch, NIH, Bethesda, MD 20892, USA 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–Pick 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.http://bio.biologists.org/content/11/4/bio059052niemann–pick diseasetype ccerebellar ataxianpc1neurological diseasephenotype assessmentlysosomal disease |
| spellingShingle | Julia Yerger Antony C. Cougnoux Craig B. Abbott Rachel Luke Tannia S. Clark Niamh X. Cawley Forbes D. Porter Cristin D. Davidson Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 Biology Open niemann–pick disease type c cerebellar ataxia npc1 neurological disease phenotype assessment lysosomal disease |
| title | Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 |
| title_full | Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 |
| title_fullStr | Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 |
| title_full_unstemmed | Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 |
| title_short | Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1 |
| title_sort | phenotype assessment for neurodegenerative murine models with ataxia and application to niemann pick disease type c1 |
| topic | niemann–pick disease type c cerebellar ataxia npc1 neurological disease phenotype assessment lysosomal disease |
| url | http://bio.biologists.org/content/11/4/bio059052 |
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