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 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.
Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann-Pick disease, type C1
Present address: Karolinska Institutet and ScilifeLab, 171 65, Solna, Sweden
Present address: Health First Urgent Care
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): ZIA HD008988
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
- Split-screen
- Views Icon Views
- Open the PDF for in another window
-
Article Versions Icon
Versions
- Version of Record 03 May 2022
- Accepted Manuscript 22 April 2022
- Share Icon Share
-
Tools Icon
Tools
- Search Site
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. Biol Open 2022; bio.059052. doi: https://doi.org/10.1242/bio.059052
Download citation file:
Advertisement
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
Gatekeeping at BiO
In his Editorial, BiO Editor-in-Chief Dan Gorelick outlines the criteria by which articles submitted to BiO are assessed, as part of initiatives to increase transparency of journal 'gatekeeping'.
The Forest of Biologists
Our Publisher Claire Moulton recently visited the two Woodland Trust UK sites where we are planting new native trees for published Research and Review papers and protecting ancient woodland on behalf of our peer reviewers.
A Year at the Forefront
This series of Review articles aims to highlight the key discoveries, technological innovations, new resources and new hypotheses that have made an impact in a specific biological field during the past year. This publishing opportunity is available to early-career researchers, without a publication charge. Find out about eligibility and how to submit a proposal.
How we support early-career researchers
Biology Open, its sister journals and its not-for-profit publisher, The Company of Biologists, support early-career researchers in numerous ways, helping them grow their network and raise their profile. Find out what we can do to support you.