Logo
Homepage
Explore Our Models
My Cart
Contact
Subscribe
Models
Genetically Engineered Animals
Knockout Mice
Knockout Rats
Knockin Mice
Knockin Rats
Transgenic Mice
Transgenic Rats
Model Generation Techniques
Turboknockout<sup>®</sup> Gene Targeting
ES Cell Gene Targeting
Targeted Gene Editing
Regular Transgenic
PiggyBac Transgenesis
BAC Transgenic
Research Models
HUGO-GT™ Humanized Mice
Cre Mouse Lines
Humanized Target Gene Models
Metabolic Disease Models
Ophthalmic Disease Models
Neurological Disease Models
Autoimmune Disease Models
Immunodeficient Mouse Models
Humanized Immune System Mouse Models
Oncology & Immuno-oncology Models
Covid-19 Mouse Models
MouseAtlas Model Library
Knockout Cell Line Product Catalog
Tumor Cell Line Product Catalog
AAV Standard Product Catalog
Animal Supporting Services
Breeding Services
Cryopreservation & Recovery
Phenotyping Services
BAC Modification
Custom Cell Line Models
Induced Pluripotent Stem Cells (iPSCs)
Knockout Cell Lines
Knockin Cell Lines
Point Mutation Cell Lines
Overexpression Cell Lines
Virus Packaging
Adeno-associated Virus (AAV) Packaging
Lentivirus Packaging
Adenovirus Packaging
CRO Services
By Therapeutic Area
Oncology
Ophthalmology
Neuroscience
Metabolic & Cardiovascular Diseases
Autoimmune & Inflammatory
By Drug Type
AI-Powered AAV Discovery
Gene Therapy
Oligonucleotide Therapy
Antibody Therapy
Cell Immunotherapy
Resources
Promotion
Events & Webinars
Newsroom
Blogs & Insights
Resource Vault
Reference Databases
Peer-Reviewed Citations
Rare Disease Data Center
AbSeek
Cell iGeneEditor™ System
OriCell
Quality
Facility Overview
Animal Health & Welfare
Health Reports
About Us
Corporate Overview
Our Partners
Careers
Contact Us
Login
Genetic Disorders and Genomics
The Pathogenic Gene of Huntington's disease – HTT
Cyagen Technical Content Team | June 10, 2025
Explore Ready-to-Use Mouse Models in MouseAtlas
Discover our extensive library of KO, cKO, and disease-specific mouse models. Accelerate your research with study-ready animals validated by scientists worldwide.
Explore Ready-to-Use Mouse Models in MouseAtlas
Contents
01. Background Information – HTT Gene 02. Overview of HTT Gene Research 03. HTT Regulates Function of Cortico-Striatal Synapse 04. HTT Expression in Human Tissues

Huntington's disease (HD) is a rare, progressive brain disorder that is inherited in an autosomal dominant manner - this disorder is caused by a defective huntingtin (HTT) protein that changes the brain, causing patients to experience problems with behavior, thinking and involuntary movements. The HTT gene encodes the huntingtin protein and is the primary pathogenic gene of Huntington's disease. In this article we review the functionality of HTT, and explore its role in targeted gene therapy for Huntington's disease, presenting brief insights on HTT gene research.

Background Information – HTT Gene
Species Human Mouse Rat
Chromosome 4 5 14
Full Length 169,280 150,795 149,499
mRNA(nt) 13,472 12,237 13,189
Numbers of exons 67 67 68
Numbers of amino acids 3142 3120 3120
Cyagen Mouse Models
Status Custom Catalog Models Live Mice
Knockout (KO) √ √
Conditional Knockout (cKO) √

Note: the mark ‘√’ represents the corresponding models that available from Cyagen Knockout Catalog Models

>> View Our HTT Mouse Model

Overview of HTT Gene Research

A defective HTT (huntingtin) gene directly causes to the developmental pathology of Huntington disease (HD) – the gene defect involves extra repeats of a specific chemical code, CAG, in its pathogenic region (exon 1). In the normal HTT gene, there are less than 35 consecutive CAG trinucleotide repeats, encoding a polyglutamic acid, located in exon 1. When the CAG repeat number is more than 35, the incidence of HD will rise along with the increase in CAG repeat numbers. At present, the HD incidence rate among Caucasians in Europe and America is 0.005%~0.01%. Patients with HD usually present multiple behavioral difficulties, such as in movement, cognition, and emotions. Despite discovering the defective gene known to cause HD in 1993, and the subsequent in-depth research studies on HD-related neurodegeneration, there are still no therapeutic drugs for HD on the market. As researchers elucidate the functionality of huntingtin protein, there is hope that such discoveries may offer insights into a wide range of brain disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS).

The human HTT gene is located on the short arm of chromosome 4 - it has a length of 180bp and contains 67 exons. The pathogenic site of Huntington's disease is in the first exon (exon 1) of HTT, with most of the mutations being haplotype A1, A2 and A3. The important regions of huntingtin (HTT) protein include: the N-terminal polyglutamine (polyQ) region, the polyproline region, and the three HEAT regions with the most amino acids. The huntingtin protein has recognition sites for various proteasomes, Caspases, and Calpain. In normal circumstances, huntingtin can be hydrolyzed into two segments by Caspases, and the two segments can combine to perform their own functions. In HD-related pathological conditions, not only is the expression of HTT is increased and its free N-terminal products are easier to aggregate, but at the same time, the C-terminal fragments will also produce a certain degree of toxicity.

Figure 1: A) Human Huntingtin gene, HTT, and B) its protein, huntingtin (HTT), with an overview of posttranslational modifications.

ISBN: 978-0-12-805120-7

HTT Regulates Function of Cortico-Striatal Synapse

Normal HTT can promote the transcription of BDNF and the transport of BDNF in the cortex and striatum axons. When BDNF is released into the cortico-striatal synapse, the TrkB receptor in striatum will be activated, resulting in the endocytosis of TrkB. Upon the endocytosis of TrkB, Dynein, Dynactin and Kinesin-1 are recruited to form a complex that activates Erk1/2 and promotes the survival of neurons.

Figure 2. HTT Regulates the Function of the Cortico-Striatal Connection

DOI: 10.1016/j.neuron.2016.02.003。

HTT Expression in Human Tissues
Figure 3. Expression of Human HTT and mouse Htt gene mRNA (relative expression values). This gene is undoubtedly expressed at an absolute high level in human and mouse brain tissues. HTT mRNA is also highly expressed in the testis, skin, spleen, and lungs. In addition, the expression in thymus is relatively high. (The expression information is normalized relative value rather than direct PRKM data. The comparison above is normalized within the same species; exact expression level values between mice and human are not to be compared) Data source: NCBI.
With the advancement of HTT gene and huntingtin protein function research alongside rapid development of nucleic acid drugs and genetic engineering technologies, there will be more convenient, safer, and more effective therapeutic drugs that will succeed in clinical trials and move toward widespread therapeutic use.
With more than 15 years’ experience in genetic engineering, Cyagen is an established provider of custom mouse models of neurological and neurodegenerative diseases, including Huntington’s disease (HD). Cyagen is committed to enabling the development of therapeutics for neurodegenerative diseases by delivering genotype-guaranteed animal models to study disease mechanisms, target validation, drug screening and more.

Gene Therapy Related Resource:

>> Rare Disease Model Collaboration Program

>> Case Studies in Gene Therapy - Applications of Accurate Mouse Models

>> Pathogenic Genes of Rare Disease - SMN1 in Spinal Muscular Atrophy Research

>> Rare Disease Grant Awards Announced for BeHEARD Challenge

References:

1. Saudou,Frédéric,Humbert S.The Biology of Huntingtin[J].Neuron,2016,89(5):910-926.

2. Hersch SM,Rosas HD.Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s Disease.In:Lo DC,Hughes RE,editors.Neurobiology of Huntington's Disease:Applications to Drug Discovery.Boca Raton(FL):CRC Press/Taylor&Francis;2011.Chapter 11.PMID:21882408.

3. Ehrnhoefer DE,Wong BK,Hayden MR.Convergent pathogenic pathways in Alzheimer's and Huntington's diseases:shared targets for drug development.Nat Rev Drug Discov.2011 Oct 21;10(11):853-67.doi:10.1038/nrd3556.PMID:22015920;PMCID:PMC3206090.

4. ISBN: 978-0-12-805120-7

5. Saudou F, Humbert S. The Biology of Huntingtin. Neuron. 2016 Mar 2;89(5):910-26. doi: 10.1016/j.neuron.2016.02.003. PMID: 26938440.

Subscribe to Receive Updates & Promotions From Cyagen
Subscribe
* Your privacy matters to us. We never share it with third parties.
Explore More
Unveiling the Secrets of the DIO-B6-M Mouse Model for Obesity Research
Spinocerebellar Ataxia Type III (SCA3) Research Model—B6-hATXN3 Mice
Vision Stolen by Years - Age-related Macular Degeneration
Y Maze Behavioral Task: Studying the function of spatial learning and memory in Neuroscience research
Share
Top
Ready to Elevate Your Research?
Discover how Cyagen can support your research. Let’s start a conversation.
Model Library
Model Library
Resources
Resources
Animal Quality
Animal Quality
Get Support
Get Support
Address:
2255 Martin Avenue, Suite E Santa Clara, CA 95050-2709, US
Tel:
800-921-8930 (8-6pm PST)
+1408-963-0306 (lnt’l)
Fax:
408-969-0338
Email:
animal-service@cyagen.com
service@cyagen.us
CRO Services
OncologyOphthalmologyNeuroscienceMetabolic & CardiovascularAutoimmune & InflammatoryGene TherapyAntibody Therapy
About Us
Corporate OverviewOur PartnersCareersContact Us
Social Media
Disclaimer: Pricing and availability of our products and services vary by region. Listed prices are applicable to the specific countries. Please contact us for more information.
Copyright © 2025 Cyagen. All rights reserved.
Privacy Policy
Site Map
Stay Updated with the Latest from Cyagen
Get the latest news on our research models, CRO services, scientific resources, and special offers—tailored to your research needs and delivered straight to your inbox.
Full Name
Email
Organization
Country
Areas of Interest