Neurofilament cytoskeleton disruption does not modify accumulation of trophic factor mRNA.
Previously we described a transgenic mouse model in which neurofilaments are sequestered in neuronal cell bodies and withheld from the axonal compartment. This model and other transgenic models with disrupted neurofilaments are used widely to investigate the role of the neurofilament cytoskeleton in normal neurons and in inherited or acquired diseases. To interpret such studies, it is important to establish whether the maldistribution of neurofilaments has major secondary consequences on the cell biology of the affected neurons. Notably, multiple perturbations of the nervous system simultaneously affect both the neuronal cytoskeleton and neurotrophin expression. To determine whether the expression of neurotrophic factors or their receptors is perturbed by a primary disruption in neurofilaments, we compared the accumulated mRNA levels for ciliary neuroptrophic factor (CNTF), nerve growth factor, neurotrophin 3, and the alpha CNTF receptor in mature transgenic mice and their littermate controls. Consistently with the prolonged survival of neurons expressing atypical or abnormally distributed neurofilaments, no obvious changes were observed for any of the mRNA species examined.
Robert
P
P
Laboratoire de Neurobiologie et Transgénèse, UPRES-EA3143, INSERM E9928, Centre Hospitalier Universitaire, 49033 Angers, France.
Peterson
A C
AC
Eyer
J
J
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics*; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D011993:Recombinant Fusion Proteins; D020932:Nerve Growth Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases