Defects in nerve conduction velocity and different muscle fibre-type specificity contribute to muscle weakness in Ts1Cje Down syndrome mouse model.

Usman Bala,Mei-I Lai,King-Hwa Ling,Chai Ling Lim,Melody Pui-Yee Leong,Ohnmar Htwe,Hayati Kadir Shahar,Zhe-Kang Law,Khairunnisa Ramli,Pike-See Cheah,Fauziah Othman,Yann Herault

doi:10.1371/journal.pone.0197711

Abstract

BackgroundDown syndrome (DS) is a genetic disorder caused by presence of extra copy of human chromosome 21. It is characterised by several clinical phenotypes. Motor dysfunction due to hypotonia is commonly seen in individuals with DS and its etiology is yet unknown. Ts1Cje, which has a partial trisomy (Mmu16) homologous to Hsa21, is well reported to exhibit various typical neuropathological features seen in individuals with DS. This study investigated the role of skeletal muscles and peripheral nerve defects in contributing to muscle weakness in Ts1Cje mice.ResultsAssessment of the motor performance showed that, the forelimb grip strength was significantly (P<0.0001) greater in the WT mice compared to Ts1Cje mice regardless of gender. The average survival time of the WT mice during the hanging wire test was significantly (P<0.0001) greater compared to the Ts1Cje mice. Also, the WT mice performed significantly (P<0.05) better than the Ts1Cje mice in the latency to maintain a coordinated motor movement against the rotating rod. Adult Ts1Cje mice exhibited significantly (P<0.001) lower nerve conduction velocity compared with their aged matched WT mice. Further analysis showed a significantly (P<0.001) higher population of type I fibres in WT compared to Ts1Cje mice. Also, there was significantly (P<0.01) higher population of COX deficient fibres in Ts1Cje mice. Expression of Myf5 was significantly (P<0.05) reduced in triceps of Ts1Cje mice while MyoD expression was significantly (P<0.05) increased in quadriceps of Ts1Cje mice.ConclusionTs1Cje mice exhibited weaker muscle strength. The lower population of the type I fibres and higher population of COX deficient fibres in Ts1Cje mice may contribute to the muscle weakness seen in this mouse model for DS.

Highlights

Down syndrome (DS) is a genetic disorder due to the presence of an extra copy of the human chromosome 21 (Hsa21), a condition known as trisomy 21 [1]
This study investigated the role of skeletal muscles and peripheral nerve defects in contributing to muscle weakness in Ts1Cje mice
Adult Ts1Cje mice exhibited significantly (P

Summary

Introduction

Down syndrome (DS) is a genetic disorder due to the presence of an extra copy of the human chromosome 21 (Hsa21), a condition known as trisomy 21 [1] This disorder is characterised by a complex set of pathologies and several clinical phenotypes, such as intellectual disability, a characteristic set of facial features, hypotonia, cardiac defects, and anomalies associated with the immune, endocrine and digestive systems [2,3,4]. Individuals with DS display several forms of motor dysfunction, including gross and fine motor deficits, poor balance and motor coordination and movement variability [5,6] These individuals have delayed motor function development, difficulties in motor planning, perceptual motor deficits and instabilities in trunk and postural control [7,8,9] as well as stiff joints [10]. This study investigated the role of skeletal muscles and peripheral nerve defects in contributing to muscle weakness in Ts1Cje mice

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