In Vivo Models for Translation of Huntington’s Disease in Humans
We conduct contract in vivo Huntington’s disease animal studies to test the efficacy of novel therapeutics. We offer two mouse models, the Q175 mouse model, and the transgenic R6/2 mouse model, as well as rat and large animal studies. All of our studies display robust, gene dose-dependent, progressive, and early-onset alterations in the validated endpoint assays. As part of our Neuroscience and Rare Disease portfolio, we also offer a selection of validated in vitro Huntington disease assays as well.
Q175 Mouse Model
The Q175 knock-in mouse is one of our two Huntington’s disease animal models. The Q175 Mouse contains human mHTT allele with the expanded CAG repeat (~179 repeats) within the native mouse huntingtin gene. Thus, this animal model reflects an accurate representative of Huntington’s disease in humans from a genetic aspect. Both homo- and heterozygous Q175 mice exhibit first signs of motor symptoms early, from 3-4 months of age, and behavioral deficits are accompanied by marked brain atrophy and brain metabolite changes by eight months.
Transgenic R6/2 Mouse Model
Our most commonly used model is the transgenic R6/2 mouse model [B6CBA-Tg(HDexon1)62Gpb/1J]. The R6/2 mouse contains N-terminally truncated mutant HTT (mHTT) with CAG repeat expansion (~125 repeats) within the huntingtin gene exon 1. This model develops HD-like symptoms, including decreased body weight as well as motor and cognitive deficits, starting as early as 6-8 weeks of age. Survival is followed until 25 weeks of age.
Huntington’s disease animal model components:
- Body weight
- Motor deficits
- Open field test
- Rear climbing test
- Rotarod test
- Grip strength test
- Cognitive deficits
- Procedural two-choice swim test
- Contextual fear conditioning
- Neurological index
- In vivo brain imaging
- MRI for brain volumetry (whole brain, cortex, striatum)
- MRS for striatal metabolites
- Various options in mRNA and protein detection assays
Several additional endpoints are available for evaluating the lead compound method of action, such as:
- IHC for mutated Huntingtin protein
- Inflammatory markers
- Iron accumulation and dopaminergic neurotransmission for intensity analysis or stereological counting
- qPCR assays for various transcripts
Stem Cell-Derived Striatal Neurons for In Vivo Huntington’s Disease Studies
Mariangela Iovino, PhD, Group Leader of Integrated Biology at Charles River presents at Neuroscience Day 2020 and takes a deep dive in to current Huntington’s disease research with stem cell-derived striatal neurons. View additional Neuroscience Day 2020 presentations here.
Frequently Asked Questions (FAQs) for Huntington’s Disease Animal Studies
What factors are important for In Vivo Huntington’s disease animal studies?
When evaluating a potential therapeutic, it is important to have an animal model that accurately represents the neuropathology and symptomology of the disease. It is also crucial to have robust, gene dose-dependent, progressive and early-onset alterations in your study. We offer various customizable Huntington’s disease animal studies that take all of these factors into consideration.
What Huntington’s disease animal studies can I apply to my research?
Our models include the Q175 mouse, the transgenic R/62 mouse, as well as rat and large animal models. We also offer validated in vitro studies.