Smooth muscle atrophy and colon pathology in SMN deficient mice

American Journal of Translational Research

Zhaohui Yang¹  Yun Yang²  David W Hammers³  George Vassilakos⁴ 

[1] Department of Applied Physiology and Kinesiology, University of Florida College of Health and Human Performance, Gainesville, FL;Department of Gastrointestinal Surgery, West China/Chengdu Shangjin Nanfu Hospital, Sichuan University, Chengdu, Sichuan Province, China;Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL Myology Institute, University of Florida College of Medicine, Gainesville, FL;Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

关键词: Spinal muscular atrophy;    gastrointestinal dysfunction;    smooth muscle atrophy;    colon pathology;    interstitial cells of Cajal;    c-kit;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by loss of motor neurons in the ventral horn of the spinal cord. Clinical features such as progressively lethal respiratory weakness and associated muscle wasting have been extensively studied but less attention has been given to gastrointestinal (GI) dysfunction, which is common symptomatology in SMA patients with 43% constipation, 15% abdominal pain, and 14% meteorism. In the current study, the PrP92-SMN mouse model of SMA was utilized, to complement previous studies in which cells of the Enteric Nervous system (ENS) were susceptible to Smn (survival motor neuron) deficiency and could possibly be the basis of the observed GI symptoms. Necropsy of our mouse model showed impairment in feces excretion and smaller bladder mass, compared to Wild-Type (WT) animals. Along with the reduction in bladder mass, we also observed a decrease in the size of smooth muscles, due to reduction in Cross-Sectional Area (CSA). Interstitial cells of Cajal (ICC) provide important regulatory functions in the GI tract. To investigate if ICC are implicated in Smn deficient-induced colonic dysmotility, we assessed ICC distribution and abundance, by c-Kit, a well-established marker. SMA mice exhibited fewer c-Kit positive cells with altered localization, compared to WT. In conclusion, the observed histopathological abnormalities of our mouse model, can be secondary to SMN deficiency and could possibly underlie the GI symptoms observed in SMA patients. Future therapeutic approaches for SMA, must address not only CNS symptoms, but also non-motor-neuron-related symptoms. The PrP92-SMN mouse model could be a useful model for assessing therapeutic rescue of GI dysfunction in SMA.

【 授权许可】

CC BY-NC