Morphological and functional phenotyping of skeletal muscle and bone in the zQ175 knock-in mouse model of Huntington's disease.

Abstract

: Huntington's disease (HD) is a progressive neurodegenerative disorder primarily affecting the central nervous system (CNS). However, emerging evidence suggests that peripheral tissues, including skeletal muscle and bone, also undergo pathological changes contributing to disease burden.: To characterize musculoskeletal impairments in the zQ175 knock-in (KI) mouse model of HD, through integrated behavioral, biomechanical, and imaging analyses.: Motor function was assessed using grip strength, rotarod, and open field testing.contractility of the extensor digitorum longus (EDL) and Soleus (Sol) muscles was measured. Muscle fiber cross-sectional area (CSA) was quantified using semi-automated segmentation. Bone microarchitecture was analyzed using high-resolution micro-computed tomography (μCT).: Six-month-old homozygous zQ175 mice exhibited significantly reduced muscle strength and impaired contractile properties in both the EDL and Soleus muscles compared to wild-type (WT) controls. µCT analysis revealed decreased trabecular bone volume and alterations in bone structure.: These findings provide a comprehensive musculoskeletal phenotyping of zQ175 mice, revealing early-onset muscle atrophy and skeletal fragility. Our study highlights the importance of targeting peripheral manifestations in HD and establishes zQ175 KI mice as a valuable additional model for investigating systemic disease mechanisms.