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© The Rockefeller University Press, 0021-9525/2000//1169 $5.00
The Journal of Cell Biology, Volume 151, Number 6, , 2000 1169-1178

Map1b Is Required for Axon Guidance and Is Involved in the Development of the Central and Peripheral Nervous System

^a Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, University of Vienna, A-1030 Vienna, Austria
^b Department of Neuroanatomy, Max-Planck-Institute for Brain Research, D-60528 Frankfurt, Germany
^c University of Veterinary Medicine, A-1210 Vienna, Austria
^d Neuromuscular Research Department, University of Vienna, A-1090 Vienna, Austria
^e Institute for Brain Research, University of Vienna, A-1090 Vienna, Austria
Institute of Biochemistry and Molecular Cell Biology, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.43-1-4277-5285443-1-4277-52858

friedrich.propst{at}univie.ac.at

Microtubule-associated proteins such as MAP1B have long been suspected to play an important role in neuronal differentiation, but proof has been lacking. Previous MAP1B gene targeting studies yielded contradictory and inconclusive results and did not reveal MAP1B function. In contrast to two earlier efforts, we now describe generation of a complete MAP1B null allele. Mice heterozygous for this MAP1B deletion were not affected. Homozygous mutants were viable but displayed a striking developmental defect in the brain, the selective absence of the corpus callosum, and the concomitant formation of myelinated fiber bundles consisting of misguided cortical axons. In addition, peripheral nerves of MAP1B-deficient mice had a reduced number of large myelinated axons. The myelin sheaths of the remaining axons were of reduced thickness, resulting in a decrease of nerve conduction velocity in the adult sciatic nerve. On the other hand, the anticipated involvement of MAP1B in retinal development and -aminobutyric acid C receptor clustering was not substantiated. Our results demonstrate an essential role of MAP1B in development and function of the nervous system and resolve a previous controversy over its importance.

Key Words: microtubule-associated protein 1B • brain development • gene targeting • corpus callosum • myelin

© 2000 The Rockefeller University Press

Abbreviations used in this paper: GABA, -aminobutyric acid; IPL, inner plexiform layer; MAP, microtubule-associated protein.

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