title: C-kit is important for SOD1(G93A) mouse survival independent of mast cells.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease leading to progressive and lethal paralysis. The disease process is multi-factorial and is characterized by selective motor neuron degeneration. Previous work demonstrated that the local concentration of various growth factors can influence motor neuron survival and disease progression. A potential role for c-kit, a growth factor receptor present in the spinal cord, in ALS is unknown. To dissect the role of c-kit in ALS we interbred SOD1(G93A) mice with kit(w-sh/w-sh) mice, which have a 70% decrease in c-kit expression in the spinal cord. kit(w-sh/w-sh) SOD1(G93A) mice have a reduced survival compared to SOD1(G93A) mice, while the amount of motor neurons at end stage is similar. By means of grip strength and nerve conductance analysis we show that kit(w-sh/w-sh) mice have diminished strength and slightly impaired compound muscle action potential latency, although the number of neurons is similar across genotypes. Decreasing kit gene expression in SOD1(G93A) mice is detrimental and our results imply that this effect is independent of mast cells, as tested by ketotifen administration. To conclude, our data expand on the protective role of growth factors in ALS, as decreasing c-kit by approximately 70% is detrimental in SOD1(G93A) mice.
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium; Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: K A
authors.initials: KA
authors.lastname: Staats
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Schönefeldt
authors.affiliation: Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Helleputte
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium; Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Van Rillaer
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Lampi
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Dooley
authors.affiliation: Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium. Electronic address: Ludo.VandenBosch@vib-kuleuven.be.
authors.forename: L
authors.initials: L
authors.lastname: Van Den Bosch
authors.affiliation: Translational Immunology Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven 3000, Belgium. Electronic address: adrian.liston@vib.be.
authors.forename: A
authors.initials: A
authors.lastname: Liston
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D006634:Histamine H1 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009431:Neural Conduction / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D006634:Histamine H1 Antagonists; D012333:RNA, Messenger; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D019009:Proto-Oncogene Proteins c-kit; D007665:Ketotifen
keywords: amyotrophic lateral sclerosis; c-kit; ketotifen; mast cells; motor neurons; stem cell factor receptor