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Paramutation-like effects at the mouse scapinin (Phactr3) locus.

J. Mol. Biol.2008 Mar 28;377(3):605-8. Epub 2008 Jan 31
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摘要


Paramutation-like phenomena have been extensively studied in plants and so far described for a very few engineered loci in the mouse. Here we report an allele-specific expression analysis of the Phactr3 (phosphatase and actin regulator 3) locus by identifying the first internal mouse transcripts with a paramutation-like effect not associated with transgenic or knockout mice. In our previous work, we showed that the Phactr3 gene was mainly transcribed in the brain, exhibiting a complex genomic organisation with four alternatively spliced leader exons. Due to the location of the Phactr3 gene in the distal imprinting region on mouse chromosome 2, we generated a mouse model to investigate the possible parental influence on the allelic expression pattern by reciprocally mating NMRI mice and Mus musculus castaneus. We were able to identify a single-nucleotide polymorphism in leader exon 1C representing restriction fragment length polymorphism. After reverse transcription PCR, NMRI and M. musculus castaneus showed a homozygous restriction pattern according to their genotype. Unlike this, reverse transcription PCR products of the F1 hybrids of both crosses were transcribed from the NMRI allele only. Therefore, the Phactr3 exon 1C splice variant is potentially strain specific regulated, leading to the expression of only one allele of the reciprocal crosses. So far, this has not yet been described for an internal mouse gene. These results potentially provide new insight into non-Mendelian inheritance in mammals and may serve also as a model for investigating the regulation of allele-specific expression.

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