Cardiac defects contribute to the pathology of spinal muscular atrophy models

Hum Mol Genet. 2010 Oct 15;19(20):4059-71. doi: 10.1093/hmg/ddq329. Epub 2010 Aug 9.


Spinal muscular atrophy (SMA) is an autosomal recessive disorder, which is the leading genetic cause of infantile death. SMA is the most common inherited motor neuron disease and occurs in approximately 1:6000 live births. The gene responsible for SMA is called Survival Motor Neuron-1 (SMN1). Interestingly, a human-specific copy gene is present on the same region of chromosome 5q, called SMN2. Motor neurons are the primary tissue affected in SMA. Although it is clear that SMA is a neurodegenerative disease, there are clinical reports that suggest that other tissues contribute to the overall phenotype, especially in the most severe forms of the disease. In severe SMA cases, a growing number of congenital heart defects have been identified upon autopsy. The most common defect is a developmental defect referred to as hypoplastic left heart. The purpose of this report is to determine whether cardiac tissue is altered in SMA models and whether this could contribute to SMA pathogenesis. Here we identified early-stage developmental defects in a severe model of SMA. Additionally, pathological responses including fibrosis and oxidative stress markers were observed shortly after birth in a less severe model of disease. Similarly, functional differences were detected between wild-type and early-stage SMA animals. Collectively, this work demonstrates the importance of cardiac development and function in these severe models of SMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fibrosis
  • Gene Expression
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / pathology*
  • Heart Septum / embryology*
  • Heart Septum / pathology*
  • Humans
  • Hypoplastic Left Heart Syndrome / genetics
  • Hypoplastic Left Heart Syndrome / pathology
  • Mice
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Muscular Atrophy / genetics
  • Muscular Atrophy / pathology*
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Nerve Tissue Proteins / genetics
  • Oxidative Stress
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 2 Protein / genetics
  • Ventricular Remodeling


  • Nerve Tissue Proteins
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein