Selective changes in the neurofilament and microtubule cytoskeleton of NF-H/LacZ mice.
This study focused mainly on changes in the microtubule cytoskeleton in a transgenic mouse where beta-galactosidase fused to a truncated neurofilament subunit led to a decrease in neurofilament triplet protein expression and a loss in neurofilament assembly and abolished transport into neuronal processes in spinal cord and brain. Although all neurofilament subunits accumulated in neuronal cell bodies, our data suggest an increased solubility of all three subunits, rather than increased precipitation, and point to a perturbed filament assembly. In addition, reduced neurofilament phosphorylation may favor an increased filament degradation. The function of microtubules seemed largely unaffected, in that tubulin and microtubule-associated proteins (MAP) expression and their distribution were largely unchanged in transgenic animals. MAP1A was the only MAP with a reduced signal in spinal cord tissue, and differences in immunostaining in various brain regions corroborate a relationship between MAP1A and neurofilaments.
Riederer
Irène M
IM
Institut de Biologie Cellulaire et de Morphologie, Lausanne, Switzerland.
Robert
Patrick
P
Porchet
Raymonde
R
Eyer
Joël
J
Riederer
Beat M
BM
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D007123:Immunoelectrophoresis, Two-Dimensional; D007150:Immunohistochemistry; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000502:physiology; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014404:Tubulin / Q000502:physiology
D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D025542:Neurofibromin 1; D016900:Neurofilament Proteins; D014404:Tubulin; C044882:neurofilament protein L; C085348:tau-1 monoclonal antibody; C051774:neurofilament protein H; C061195:neurofilament protein M