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

TLDR

Microtubule‑associated protein MAP1B has long been suspected to influence neuronal differentiation, yet prior gene‑targeting studies were contradictory and inconclusive, leaving its role unclear. The study aims to generate a complete MAP1B null allele to clarify its function. The authors created a full MAP1B knockout allele through targeted gene disruption. Homozygous MAP1B‑null mice are viable but lack a corpus callosum, have misdirected cortical axons, reduced large myelinated peripheral axons with thinner sheaths and slower conduction, while heterozygotes are normal; retinal development and GABA_A receptor clustering are unaffected, confirming MAP1B’s essential role in nervous system development and function.

Abstract

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 γ-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.