Tg(Mpz*L106I)1Msch

The transgenic construct contains a mutant form of the mouse peripheral myelin protein zero (Mpz) gene that replicates the human "P0sub" mutation associated with a severe, early onset, tumaculous form of Charcot-Marie-Tooth disease Type 1B (CMT1B). The construct comprises 6 kb of 5' flanking sequence, all exons and introns, and the Mpz polyadenylation signal; the mutation is an A to T transversion at nucleotide position 1644 (from the translation initiating ATG) that results in replacement of leucine by isoleucine at amino acid position 106 of the protein (L106I). Analysis of total sciatic nerve RNA from transgenic mice by RT-PCR followed by digestion with an endonuclease for which the mutation introduces a new recognition site demonstrated 6-fold greater expression of the mutant than of the endogenous transcript. In contrast, the proportion of protein zero (P0)/total protein in whole sciatic nerve homogenates from transgenic mice, as measured by immunoblot analysis, is ~10-fold lower than in nerves from wild-type mice. In the myelin fraction of peripheral (sciatic, femoral and dorsal root) nerve homogenates from transgenic mice of line 1, the proportion of P0/total protein is ~5-fold lower than in myelin from nerves of wild-type mice. (J:91162)