Htt-flox Mouse

HTT, encoding the huntingtin protein, is of great significance. An abnormal expansion of a glutamine stretch (polyQ) in the N-terminal sequence of the huntingtin protein, caused by a CAG repeat expansion in exon 1 of the HTT gene, leads to the devastating neurodegenerative disorder Huntington's disease (HD) [1,2,3,4,5,7,8]. HTT is ubiquitously expressed at both tissue and subcellular levels, interacting with many partners, yet its cellular function has long been ill-defined [1].

Using HD knock-in mice expressing full-length mutant HTT with a 140-glutamine repeat at the endogenous level, studies showed that the numbers of astrocytes and oligodendrocytes were not significantly altered in postnatal HD KI mice compared to wild-type mice. However, at 3 months of age, myelin protein expression was reduced, and myelin thickness of axons was slightly but significantly decreased in HD KI mice, suggesting that cytoplasmic mutant HTT mediates myelination defects in the early disease stage without affecting glial cell differentiation and maturation [6].

In conclusion, HTT is closely associated with Huntington's disease. The study of HD knock-in mouse models reveals that mutant HTT may have a specific impact on myelination in the early stage of the disease, providing insights into the pathological mechanisms of HD. This helps in understanding the role of HTT in normal and disease-related biological processes, and may contribute to the development of therapeutic strategies for Huntington's disease.