title: Paralytic tremor (pt): a new allele of the proteolipid protein gene in rabbits.
abstract: Paralytic tremor (pt) is a sex-linked mutation in rabbit that affects myelination of the CNS. Myelin in the pt brains represents approximately 30% of the normal levels. Previously we showed that the pt mutation affects primarily proteolipid protein (Plp) gene expression. In the present study we investigated the relative effect of the pt mutation on two distinctive Plp gene products, PLP- and DM-20-specific messenger RNAs. Our results showed that both PLP and DM-20 are affected and that the ratio DM-20/PLP was higher in pt rabbits than in age-matched controls. We sequenced normal rabbit PLP cDNA and characterized pt mutation at the DNA level. Rabbit PLP sequence, deduced from cDNA, differs from the human protein only at Thr198. Sequence analysis of the mutant cDNA revealed a transversion T-->A in exon 2 of the Plp gene. This point mutation, which is placed at the end of the first potential transmembrane domain, results in a substitution of His36 by a glutamine. This transversion abolishes a restriction site that enabled us to screen a large number of animals and observe a perfect correlation between the pt allele and the abnormal phenotype.
authors.affiliation: Department of Pediatrics, CHUV, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Tosic
authors.forename: M
authors.initials: M
authors.lastname: Dolivo
authors.forename: K
authors.initials: K
authors.lastname: Domańska-Janik
authors.forename: J M
authors.initials: JM
authors.lastname: Matthieu
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017385:Sequence Homology; D012730:Sex Chromosomes
chemical_list: D018076:DNA, Complementary; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger