Artikel
Muscle and nerve pathology in spinal muscular atrophy with respiratory distress (SMARD1). Comparison of human and murine SMARD
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Autoren
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Gisela Stoltenburg-Didinger
- Universitätsmedizin Berlin, Institute of Cell and Neurobiology, Berlin, Germany
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Sibylle Jablonka
- University of Wuerzburg, Institute of Clinical Neurobiology, Wuerzburg, Germany
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Angela Kaindl
- Universitätsmedizin Berlin, Institute of Cell and Neurobiology, Berlin, Germany; Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
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Katja von Au
- Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
| Veröffentlicht: | 11. September 2012 |
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Gliederung
Text
Spinal muscular atrophy with respiratory distress 1 (SMARD1) is an autosomal recessive motor neuron disorder that affects infants. The hallmarks of the disease are severe spinal muscular atrophy and diaphragmatic paralysis. SMARD1 is caused by mutations in theIGHMBP2gene, which encodes the immunoglobulin µ-binding protein 2 (Grohmann et al. 2001, 2004). A splice-site mutation in mouseighmbp2is responsible for spinalmuscular atrophy in the neuromuscular degeneration (nmd) mouse, which serves as the animal model of SMARD1 (Cook et al. 1995, Cox et al. 1998).
We had the opportunity to investigate by routine histology, immunohistochemistry and electron microscopy biopsy and autopsy specimens of skeletal muscle and peripheral nerves of 11 patients of 7 different countries. The nmd-mice were investigated at the age of 6, 8 and 10 weeks in comparison to C57BL/6 wild type of the same age.
In the patients, histopathological investigation revealed reduction of diameter in myelinated axons and Wallerian degeneration in the motor and sensory nerves (n=7). The motor endplates were devoid of axon terminals, whereas the subsynaptic cleft was well developed and preserved (Diers et al. 2005). A similar process could also be shown in the nmd mouse.
In the patients and the nmd mice, myopathic and neurogenic changes of skeletal muscle and diaphragm were present. In the mutant mice, necrosis, regeneration and reinnervation of muscle prevail. In the patients, denervation of skeletal mucle and diaphragm is the main feature.
These findings corroborate SMARD1 as a primary neurodegenerative disorder and highlight a possibly important role of IGHMBP2 protein not only for neuronal survival, but also in the muscle.
