Degeneration of neural cells in the central nervous system of mice deficient in the gene for the adhesion molecule on Glia, the beta 2 subunit of murine Na,K-ATPase.
We generated mice, null mutant in the adhesion molecule on glia (AMOG), the beta 2 subunit of the murine Na,K-ATPase gene. These mice exhibit motor incoordination at 15 d of age, subsequently tremor and paralysis of extremities, and die at 17-18 d after birth. At these ages, the mutants have enlarged ventricles, degenerating photoreceptor cells, and swelling and degeneration of astrocytic endfeet, leading to vacuoles adjoining capillaries of brain stem, thalamus, striatum, and spinal cord. In tissue homogenates from entire brains of 16-17-d-old mutants, Na,K-ATPase activity and expression of the beta 1 subunit of the Na,K-ATPase and of the neural adhesion molecules L1, N-CAM, and MAG appear normal. We suggest that the mutant phenotype can be related primarily to reduced pump activity, with neural degeneration as a possible consequence of osmotic imbalance.
Magyar
J P
JP
Department of Neurobiology, Swiss Federal Institute of Technology, Zurich.
Bartsch
U
U
Wang
Z Q
ZQ
Howells
N
N
Aguzzi
A
A
Wagner
E F
EF
Schachner
M
M
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D002560:Cerebrovascular Circulation; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D046911:Macromolecular Substances; D051379:Mice; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009043:Motor Activity; D009410:Nerve Degeneration; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014617:Vacuoles / Q000648:ultrastructure
C504191:Atp1b2 protein, mouse; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase