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

## TL;DR

This study examines muscle and bone changes in a mouse model of Huntington's disease, finding early signs of muscle weakness and bone loss.

## Contribution

The study provides a detailed musculoskeletal characterization of the zQ175 mouse model of HD, highlighting peripheral tissue changes.

## Key findings

- zQ175 mice show reduced muscle strength and impaired contractile properties in EDL and Soleus muscles.
- µCT analysis reveals decreased trabecular bone volume and structural alterations in zQ175 mice.
- Findings suggest early-onset muscle atrophy and skeletal fragility in the zQ175 model of HD.

## Abstract

Background: 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. Objective: To characterize musculoskeletal impairments in the zQ175 knock-in (KI) mouse model of HD, through integrated behavioral, biomechanical, and imaging analyses. Methods: Motor function was assessed using grip strength, rotarod, and open field testing. Ex vivo 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). Results: 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. Conclusions: 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.