FVB-HTT KI (nQ) Mouse

Huntingtin (HTT) is a disease-associated gene that is 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 the 5’ UTR, which forms a polyglutamine (polyQ) tract during translation. Huntington’s disease (HD) 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 expands 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. This ultimately affects 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 gene knock-in mouse model generated by gene editing technology, in which a mutated human HTT gene sequence carrying over 100 CAG repeats is inserted into the mouse genome. Mice carrying these mutations have been reported to exhibit pathological characteristics and functional impairment phenotypes of Huntington’s disease, and can be used for the development and screening of therapeutic drugs for Huntington’s disease, as well as for safety evaluation ^[3]. The detection data show that this model can successfully express the mutated human HTT gene and protein.