title: Insertion of an intracisternal A particle retrotransposon element in plasma membrane calcium ATPase 2 gene attenuates its expression and produces an ataxic phenotype in joggle mutant mice.
abstract: Using forward genetic analysis, we identified the insertion of an intracisternal A particle (IAP) retrotransposon element in the plasma membrane calcium ATPase 2 gene (Pmca2/Atp2b2) in the joggle mouse, a novel mutant that displays ataxic gait by postnatal day 12. Expression of Pmca2 mRNA in the joggle mouse is only 5% of that in the wild type mouse. The insertion is located 15 bp downstream of the donor splice site of the exon containing the initiation codon. Chimeric mRNA composed of the 5'-region of Pmca2 and the IAP element were detected, indicating that some of the primary transcripts are terminated by polyadenylation signals in long terminal repeats of the IAP element. We also identified cryptic splice sites in the IAP element that are likely involved in aberrant splicing of the Pmca2 primary transcripts that leads to rapid degradation of mRNA through nonsense mediated mRNA decay. Ataxia was observed in compound heterozygous mice carrying the joggle mutation and the wriggle mutation, a previously reported missense Pmca2 mutant. Thus, we attributed ataxia in joggle mice to reduced expression of Pmca2, resulting from insertion of the IAP element.
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Xiao-yang
authors.initials: XY
authors.lastname: Sun
authors.forename: Zi-yan
authors.initials: ZY
authors.lastname: Chen
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kanou
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takagishi
authors.forename: Sen-ichi
authors.initials: S
authors.lastname: Oda
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D015870:Gene Expression; D007426:Genes, Intracisternal A-Particle / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D010641:Phenotype; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018626:Retroelements; D053499:Plasma Membrane Calcium-Transporting ATPases