title: Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates.
abstract: Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. Although the majority of affected individuals survive 3-5 years following diagnosis, some subgroups experience a more rapidly progressing form, surviving less than 1 year, and other subgroups experience slowly progressing forms, surviving nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to the case for humans, variation in survival within the mSOD1 mouse has been well documented, but different progression rates have not been investigated. The present study identifies two subgroups of B6SJL mSOD1(G93A) mice with different disease progression rates, a fast progression group (FPG) and slow progression group, as evidenced by differences in the rate of motor function decline. In addition, increased disease-associated gene expression within the FPG facial motor nucleus confirmed the presence of a more severe phenotype. We hypothesize that a more severe disease phenotype could be the result of 1) an earlier onset of axonal disconnection with a consistent degeneration rate or 2) a more severe or accelerated degenerative process. We performed a facial nerve transection axotomy in both mSOD1 subgroups prior to disease onset as a method to standardize the axonal disconnection. Instead of leading to comparable gene expression in both subgroups, this standardization did not eliminate the severe phenotype in the FPG facial nucleus, suggesting that the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups are representative of the rapid and slow disease phenotypes often experienced in ALS.
authors.affiliation: Neuroscience Program, Loyola University Medical Center, Maywood, Illinois, 60153.|Research and Development Service, Hines Veterans Administration Hospital, Hines, Illinois, 60141.|Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Haulcomb
authors.affiliation: Neuroscience Program, Loyola University Medical Center, Maywood, Illinois, 60153.|Research and Development Service, Hines Veterans Administration Hospital, Hines, Illinois, 60141.
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Mesnard-Hoaglin
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Batka
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.|Program in Medical Neurosciences, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
authors.forename: Rena M
authors.initials: RM
authors.lastname: Meadows
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Miller
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Mcmillan
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Brown
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, 43210.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.|Research and Development Service, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, 46202.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Jones
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005154:Facial Nerve / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology; D061346:Laser Capture Microdissection; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000068079:Motor Disorders / Q000209:etiology; D053580:Muscle Strength / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012678:Sensation Disorders / Q000209:etiology; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: ALS; MN; disease progression; facial nerve axotomy; gene expression; mSOD1; motoneuron