Sensorimotor functions in transgenic mice expressing the neurofilament/heavy-LacZ fusion protein on two genetic backgrounds.
NFH-LacZ transgenic mice are characterized by expression of a non-endogenous fusion protein between a truncated form of mouse NFH (neurofilament of heavy molecular weight) and the complete Escherichia coli beta-galactosidase protein. These transgenic mice were compared to their respective controls on two background strains (C3H and FVB) in several sensorimotor tests. NFH-LacZ mice were deficient in tests requiring balance and equilibrium in a manner generally independent of genetic background. In particular, NFH-LacZ mice fell more quickly than controls from two stationary beams and had fewer rears in an open-field. The transgenic mice were also impaired during the initial trials of sensorimotor learning on the rotorod. We conclude that despite the absence of overt signs of sensorimotor weakness in their home cage, the disruption of the NFH gene, causing neurofilament accumulations in the cell body and diminished axonal calibers of motoneurons, is sufficient to cause motor deficits that resemble the early stages of amyotrophic lateral sclerosis.
Dubois
M
M
Université de Rouen, Faculté des Sciences, UPRES PSY.CO-1780, Laboratoire de Neurobiologie de l'Apprentissage, Mont-Saint-Aignan, France.
Strazielle
C
C
Eyer
J
J
Lalonde
R
R
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D005260:Female; D008297:Male; D018782:Maze Learning; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000175:diagnosis / Q000503:physiopathology*; D016900:Neurofilament Proteins / Q000235:genetics*; D009949:Orientation; D010641:Phenotype; D011597:Psychomotor Performance; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics*; D013037:Spatial Behavior; D001616:beta-Galactosidase / Q000235:genetics*
D016900:Neurofilament Proteins; D011993:Recombinant Fusion Proteins; C051774:neurofilament protein H; D001616:beta-Galactosidase