Molecular features of a Huntington's disease knock-in minipig - PubMed
4 hours ago
- #Huntington's disease
- #molecular features
- #knock-in minipig
- A knock-in minipig model (KI-85Q-HD) was created with an expanded CAG repeat in the HTT gene to mimic Huntington's disease molecular features.
- Somatic repeat expansion showed moderate, tissue-specific, and age-dependent increases, highest in caudate nucleus, kidney, and spleen, and detectable in blood.
- Aberrant HTT1a transcripts, due to cryptic polyadenylation in intron 1, were confirmed, along with soluble full-length mutant HTT and HTT1a proteins in brain and peripheral tissues.
- Aggregated HTT1a protein was specifically detected only in the cortex, indicating selective accumulation.
- The model exhibits pre-symptomatic Huntington's disease characteristics and may serve as a platform for therapeutic evaluation.