title: Caspase 6 has a protective role in SOD1(G93A) transgenic mice.
abstract: In amyotrophic lateral sclerosis (ALS), it has been suggested that the process of neurodegeneration starts at the neuromuscular junction and is propagated back along axons towards motor neurons. Caspase-dependent pathways are well established as a cause of motor neuron death, and recent work in other disease models indicated a role for caspase 6 in axonal degeneration. Therefore we hypothesised that caspase 6 may be involved in motor neuron death in ALS. To investigate the role of caspase 6 in ALS we profiled protein levels of caspase-6 throughout disease progression in the ALS mouse model SOD1(G93A); this did not reveal differences in caspase 6 levels during disease. To investigate the role of caspase 6 further we generated a colony with SOD1(G93A) transgenic mice lacking caspase 6. Analysis of the transgenic SOD1(G93A); Casp6(-/-) revealed an exacerbated phenotype with motor dysfunction occurring earlier and a significantly shortened lifespan when compared to transgenic SOD1(G93A); Casp6(+/+) mice. Immunofluorescence analysis of the neuromuscular junction revealed no obvious difference between caspase 6(+/+) and caspase 6(-/-) in non-transgenic mice, while the SOD1(G93A) transgenic mice showed severe degeneration compared to non-transgenic mice in both genotypes. Our data indicate that caspase-6 does not exacerbate ALS pathogenesis, but may have a protective role.
authors.affiliation: Centre for the Study of Neurological Disorders, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland; Department of Physiology and Medical Physics, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Marion C
authors.initials: MC
authors.lastname: Hogg
authors.affiliation: Centre for the Study of Neurological Disorders, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland; Department of Physiology and Medical Physics, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Mollie R
authors.initials: MR
authors.lastname: Mitchem
authors.affiliation: Centre for the Study of Neurological Disorders, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland; Department of Physiology and Medical Physics, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: König
authors.affiliation: Centre for the Study of Neurological Disorders, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland; Department of Physiology and Medical Physics, Royal College of Surgeons In Ireland, St. Stephen's Green, Dublin 2, Ireland. Electronic address: prehn@rcsi.ie.
authors.forename: Jochen H M
authors.initials: JH
authors.lastname: Prehn
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D053178:Caspase 6 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1; D053178:Caspase 6
keywords: ALS; Apoptosis; Axonal degeneration; Caspases; Neuromuscular junction; SOD1(G93A)