Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders

Dev Biol. 2014 Nov 1;395(1):84-95. doi: 10.1016/j.ydbio.2014.08.026. Epub 2014 Aug 28.


Peroxisome biogenesis disorders (PBD) are autosomal recessive disorders in humans characterized by skeletal, eye and brain abnormalities. Despite the fact that neurological deficits, including peripheral nervous system (PNS) defects, can be observed at birth in some PBD patients including those with PEX10 mutations, the embryological basis of the PNS defects is unclear. Using a forward genetic screen, we identified a mouse model for Pex10 deficiency that exhibits neurological abnormalities during fetal development. Homozygous Pex10 mutant mouse embryos display biochemical abnormalities related to a PBD deficiency. During late embryogenesis, Pex10 homozygous mutant mice experience progressive loss of movement and at birth they become cyanotic and die shortly thereafter. Homozygous Pex10 mutant fetuses display decreased integrity of axons and synapses, over-extension of axons in the diaphragm and decreased Schwann cell numbers. Our neuropathological, molecular and electrophysiological studies provide new insights into the embryological basis of the PNS deficits in a PBD model. Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit.

Keywords: Acetylcholine receptor; Axon integrity; Neuromuscular junction; Peroxisome; Synapse formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Disease Models, Animal*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Embryo, Mammalian / ultrastructure
  • Humans
  • Immunohistochemistry
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Motor Activity / genetics
  • Motor Endplate / physiology
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / innervation
  • Peripheral Nervous System Diseases / embryology
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / metabolism
  • Peroxins
  • Peroxisomal Disorders / embryology
  • Peroxisomal Disorders / genetics*
  • Peroxisomal Disorders / metabolism
  • Peroxisomes / metabolism
  • Peroxisomes / ultrastructure
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sciatic Nerve / embryology
  • Sciatic Nerve / metabolism
  • Sequence Homology, Amino Acid
  • Spinal Cord Diseases / embryology
  • Spinal Cord Diseases / genetics
  • Spinal Cord Diseases / metabolism


  • PEX10 protein, mouse
  • Peroxins
  • Receptors, Cytoplasmic and Nuclear

Supplementary concepts

  • Peroxisome biogenesis disorders