title: A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice.
abstract: Cu/Zn SOD1(G93A) transgenic mice develop phenotypical hallmarks of ALS and serve therefore as an established model to study the molecular mechanisms underlying this disease. Recent reports demonstrate that mutations in the motor protein dynein in Legs at odd angles (Loa) and Cramping (Cra1) mice lead to similar but milder phenotypes. Surprisingly, double transgenic mice (Loa/SOD1(G93A)) have been recently shown to attenuate rather than to accelerate the phenotypical expression of motor neuron degeneration. These results raise the question whether other functional relevant mutations in dynein cause a similar effect. To address this question, we have cross-bred SOD1(G93A) with Cra1/+ mice. These double transgenic mice show an attenuated decline of both motor activity and body weight and an increase of survival time compared to SOD1(G93A) mice. Thus, this study confirms that mechanisms associated with dynein such as retrograde axonal transport may play an important role in SOD1(G93A-) toxicity on motor neurons.
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Teuchert
authors.forename: D
authors.initials: D
authors.lastname: Fischer
authors.forename: B
authors.initials: B
authors.lastname: Schwalenstoecker
authors.forename: H-J
authors.initials: HJ
authors.lastname: Habisch
authors.forename: T M
authors.initials: TM
authors.lastname: Böckers
authors.forename: A C
authors.initials: AC
authors.lastname: Ludolph
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004398:Dyneins / Q000145:classification / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D016472:Motor Neuron Disease / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009410:Nerve Degeneration / Q000503:physiopathology*; D011930:Reaction Time / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D004398:Dyneins