Many different HD mouse models are now available and choosing which to use is a critical consideration that depends upon the specific research question being addressed. An important part of CHDI’s mission is to act as a ‘collaborative enabler’ in HD research, and integral to that is the establishment and maintenance of standardized genetically-modified animal (GMA) HD models as a central resource.
CHDI, The Jackson Laboratory (JAX) and PsychoGenics Inc. have compiled A Field Guide to Working with Mouse Models of Huntington’s Disease to give HD researchers an understanding of the different HD mouse models and to provide guidance to optimize their use in preclinical research and development. It describes many aspects of the established and emerging mouse models and proposes standardized best practices to facilitate direct comparison of results across laboratories. In particular, the field guide emphasizes the importance of understanding how different models reflect disease-related phenotypes and mechanisms. The intent is to improve the translation of results to the clinic and to accelerate the pace of HD therapeutic research.
This field guide is intended as a collective HD community resource that will be updated periodically and we welcome feedback from all HD researchers to improve and broaden content. Topics covered include:
- Current and emerging mouse models for HD research
- Quality control criteria and recommended best practice for using HD mouse models
- Model characteristics and considerations
- Best practice for using HD mouse models to test compound effects
Characterization of the Htt CAG-allelic mouse series
CHDI and collaborators have undertaken a project to characterize a GMA Htt CAG-allelic series of mouse strains, including RNAseq, proteomics, and behavioral data (https://pubmed.ncbi.nlm.nih.gov/29324753/; https://pubmed.ncbi.nlm.nih.gov/26900923/; https://pubmed.ncbi.nlm.nih.gov/27376585/). The raw data can be found at HDinHD, which features open-source science for the HD research community. Sign up for an account at HDinHD to access the data (much of it unpublished), computational models, and analytical tools.
Frequently Asked Questions
Where can I find a list of all HD-related mouse models?
Consult the table of mouse models in the Field Guide to Working with Mouse Models of Huntington’s Disease, or visit the Mouse Genome Informatics or International Mouse Strain Resource websites (see below) for information on whether and where lines are available.
I’m a CHDI-supported researcher, how do I obtain mouse models for my research?
CHDI-supported collaborators should contact the CHDI science director associated with their project so animals appropriate to your research can be facilitated through CHDI.
I’m an HD researcher not supported by CHDI funding, how do I order mouse models for my research?
You can order mice directly through JAX customer service; the data sheet for each mouse line has a link to order. For models not found at the JAX website, visit the Mouse Genome Informatics or International Mouse Strain Resource websites to locate the line of interest.
I maintain an HD mouse colony and want to determine/confirm the Htt CAG allele size(s), what is the best practice method or service to do this?
CHDI currently uses a genotyping service provided by Laragen Inc. to determine Htt CAG allele sizes in its mouse colonies.
Does CHDI maintain/provide other mammalian HD models in addition to the mouse (such as rat or other species) and, if so, how can I obtain information and/or access to these models?
Please contact CHDI directly at firstname.lastname@example.org for more information.
CHDI and The Jackson Laboratory (JAX) have been longstanding collaborators. While JAX offers many of the same HD mouse lines as CHDI, they also have a large number of GMAs associated with HD research that have been donated by various institutions.
International Mouse Strain Resource
A multi-institutional international collaboration supporting the use of mouse models to study human biology and disease, with an online catalog of mouse resources available globally.
International database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human health and disease.
Research tool registration and submission for CHDI collaborators
To obtain a CHDI ID (CHDI#), collaborators must submit a CHDI Foundation Materials Registration/Submission Request and complete the questionnaire; requests will take at least 10 business days to process. If you have any questions please contact the science director associated with your collaboration.