FVB-hHTT Q150 KI Mice

Catalog Number: I001019

Strain Name: FVB/NJCya-Htttm1(hHTT*Q150)/Cya

Genetic Background: FVB/NJCya

Reproduction: Heterozygote × WT

 

Strain Description

Huntingtin (HTT) is a disease-associated gene widely expressed in various tissues and organs, including the central nervous system, and is essential for normal development. The coding region of the HTT gene contains a polymorphic trinucleotide (cytosine-adenine-guanine, CAG) repeat sequence near its 5' end, which forms a polyglutamine (polyQ) tract during translation. Huntington's disease is a neurodegenerative disorder characterized by the loss of striatal neurons, caused by the aberrant expression of the CAG repeat sequence in the HTT gene. When the CAG repeat is expanded beyond 35 copies, it leads to abnormal polyQ expansion, resulting in incorrect folding of HTT protein fragments, dysregulation of protein-protein interactions, and accumulation in the cell nucleus and neuronal terminals, ultimately affecting neural signaling, intracellular protein transport, and mitochondrial function[1]. Currently, there are no effective drugs or methods to prevent or treat Huntington's disease, and there is a great need for further research into its mechanisms and the development of therapeutic approaches[2].

This strain is an hHTT Q150 knock-in mouse model generated by gene editing technology, in which a mutated human HTT gene sequence carrying 150 CAG repeats is inserted into the mouse genome. Literature reports have shown that these mice exhibit pathological features and functional impairments characteristic of Huntington's disease, and are suitable for developing and screening therapeutic drugs for Huntington's disease as well as for safety evaluation. The heterozygous FVB-hHTT Q150 KI mice are viable and fertile.

Strain Strategy

A mutated human HTT gene sequence carrying 150 CAG repeats was knocked into the mouse Htt gene Exon 1.


Strain Application

  • Development and screening of therapeutic drugs for Huntington's disease;
  • Evaluation of therapeutic drug efficacy and safety for Huntington's disease;
  • Research on the pathogenesis of Huntington's disease.

 

Validation Data

1. Grip strength, rotarod, and open field test


Figure 1. The grip strength, rotarod, and open field analysis of hHTT-Q150 KI mice at 14 months. Compared to WT mice, both male and female hHTT-Q150 mice exhibited decreased grip strength and reduced latency on the rotarod, indicating impaired locomotor activity and coordination. Additionally, the reduction in distance traveled and the percentage of time spent in the center further confirm deficits in locomotor activity and an increase in anxiety levels.

 

References
[1]Walker FO. Huntington's disease. Lancet. 2007 Jan 20;369(9557):218-28.
[2]McColgan P, Tabrizi SJ. Huntington's disease: a clinical review. Eur J Neurol. 2018 Jan;25(1):24-34.
[3]Crook ZR, Housman D. Huntington's disease: can mice lead the way to treatment? Neuron. 2011 Feb 10;69(3):423-35.