ACCELERATED DEMYELINATION OF PERIPHERAL-NERVES IN MICE DEFICIENT IN CONNEXIN-32 AND PROTEIN ZERO

Mutant mice that Hack either protein zero (P0) or connexin 32 (Cx32) w ere generated previously to investigate the function of these myelin p roteins in peripheral nerves and tee assess the value of these mice as animal models for hereditary human peripheral neuropathies. Mice that are completely devoid of P0 expression (P0(0/0)) show a complex pheno type that is characterized by hypomyelination, compromised myelin comp action, and degeneration of myelin and axons early in hfe, In contrast , young mouse mutants that have retained one wild-tape allele of the P 0 gene (P0(+/0)) reveal morphologically normal myelin hut start to dev elop signs of demyelination and remyelination at 4 months of age, A si milar late-onset myelin deficiency was observed in Cx32-deficient mice (Cx32(0/0)). We have now generated mice deficient for Cx32 and P0. In animals that lack both proteins (Cx32(0/0)/P0(0/0)), the phenotype is morphologically identical to mice that solely lack P0. Animals that l ack Cx32 and carry one functional P0 allele (Cx32(0/0)/P0(+/0)) reveal ed demyelination and remyelination as evidenced by thin myelin and Sch wann cell onion bulb formation already at the age of 4 weeks, a time p oint when no pathology was observed in the single mutants, These morph ological deficits were also more prominent in 4-month-old Cx32(0/0)/P0 (+/0) animals compared to the single mutants, Our data support the vie w that Cx32 and P0 are crucial molecules for the maintenance of myelin , Furthermore, the function of Cx32 in the peripheral nervous system a ppears to be largely dispensable when myelin compaction is impaired. ( C) 1998 Wiley-Liss, Inc.