PMC:1892049 / 4453-6058 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/1892049","sourcedb":"PMC","sourceid":"1892049","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1892049","text":"Literature searches revealed that among disease lines mapped to 6qE1, the spontaneous mutant opt mouse displays a strikingly similar presentation to that described here [1]. The underlying genetic lesion causing the opt phenotype is a homozygous in-frame deletion of exons 43 and 44 of the gene Itpr1 (Itpr1opt /opt), encoding inositol 1,4,5-triphosphate receptor 1 (Itpr1). Sequencing of all exons and intron–exon boundaries of Itpr1 in affected mice from the current study revealed a single mutation within Itpr1: a novel in-frame deletion of 18 bp within exon 36 (Itpr1Δ18/Δ18). To confirm the pathogenicity of this mutation we crossed heterozygous mice from the current study (Itpr1wt/Δ18) with mice heterozygous for the opt mutation (Itpr1wt/opt). This resulted in two litters of mice with a total of four affected Itpr1opt/Δ18 pups (from a total of 15) with a phenotype indistinguishable from that of the Itpr1Δ18/Δ18 and Itpr1opt /opt mice [1]. Furthermore, this phenotype was similar, although less severe, to that described in a mouse line with targeted deletion of Itpr1, where ataxia was described as a prominent feature [4]. As with the Itpr1opt /opt mice, where the deletion of exons 43 and 44 is also predicted to leave the translational reading frame unaffected, the in-frame Itpr1Δ18/Δ18 deletion mutation results in markedly decreased levels of Itpr1 in cerebellar Purkinje cells. In these two spontaneous mutants [1] and in the Itpr1-deficient mouse [4] generated by gene targeting, decreased Itpr1 expression is associated with the same autosomal recessive movement disorder (Figure 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