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. 2000 Oct;20(5):553–567. doi: 10.1023/A:1007059827541

Identification of a Novel Gene Encoding a PrP-Like Protein Expressed as Chimeric Transcripts Fused to PrP Exon 1/2 in Ataxic Mouse Line with a Disrupted PrP Gene

Aimin Li 1, Suehiro Sakaguchi 1, Ryuichiro Atarashi 1, Bhabesh C Roy 1, Ryota Nakaoke 1, Kazuhiko Arima 1, Nobuhiko Okimura 1, Juraj Kopacek 1,2, Kazuto Shigematsu 3
PMCID: PMC11537530  PMID: 10930132

Abstract

1. Mouse lines lacking prion protein (PrPC) have a puzzling phenotypic discrepancy. Some, but not all, developed late-onset ataxia due to Purkinje cell degeneration.

2. Here, we identified aberrant mRNA species in the brain of Ngsk Prnp 0/0 ataxic, but not in nonataxic Zrch Prnp 0/0 mouse line. These mRNAs were chimeric between the noncoding exons 1 and 2 of the PrP gene (Prnp) and the novel sequence encoding PrP-like protein (PrPLP), a putative membrane glycoprotein with 23% identity to PrPC in the primary amino acid structure. The chimeric mRNAs were generated from the disrupted Prnp locus of Ngsk Prnp 0/0 mice lacking a part of the Prnp intron 2 and its splice acceptor signal.

3. In the brain of wild-type and Zrch Prnp 0/0 mice, PrPLP mRNA was barely detectable. In contrast, in the brain of Ngsk Prnp 0/0 mice, PrP/PrPLP chimeric mRNAs were expressed in neurons, at a particularly high level in hippocampus pyramidal cells and Purkinje cells under the control of the Prnp promoter.

4. In addition to the functional loss of PrPC, ectopic PrPLP expression from the chimeric mRNAs could also be involved in the Purkinje cell degeneration in Ngsk Prnp 0/0 mice.

Keywords: ataxia, knockout mice, prion protein, prion protein-like protein, Purkinje cell

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