CNTF overproduction hastens onset of symptoms in motor neuron degeneration (mnd) mice.
Ciliary neurotrophic factor (CNTF) promotes the survival of motor neurons, in vitro and in vivo. Moreover, CNTF can block the degeneration of injured or diseased motor neurons in young rodents. Motor neuron degeneration (mnd) mutant mice display adult onset symptoms reflecting progressive motor debilitation and provide a model in which to test the hypothesis that CNTF can prevent the loss of these motor functions. We generated mnd mice that harbor a genomically integrated transgene, resulting in overexpression of the encoded CNTF protein in these mice. In contrast to the beneficial effects of CNTF in preventing motor neuron degeneration in other experimental paradigms, we report that overproduction of CNTF increased the rate of onset of motor disease symptoms in mnd mice and the presence of the transgene correlated with low adult body weight in mnd and wild-type genetic backgrounds.
Winter
C G
CG
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Saotome
Y
Y
Saotome
I
I
Hirsh
D
D
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D020934:Ciliary Neurotrophic Factor; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000502:physiology*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins