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Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality

Abstract

By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites1,2,3,4,5,6. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10)1,2,3,7, which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development.

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Figure 1: Targeted disruption of the Peg10 locus.
Figure 2: Peg10 knockout embryos show severe growth retardation and placental defects.
Figure 3: Rescue of Peg10 Pat-KO embryos by tetraploid wild-type extraembryonic tissues.
Figure 4: Partial pedigrees of Peg10 knockout mice and their normal imprinting status.
Figure 5: Relative expression levels of Peg10, Sgce and Ppp1r9a at different stages, as determined by quantitative RT-PCR.

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Acknowledgements

We thank M.A. Surani and S. Barton for helpful suggestions on this manuscript. We also thank S. Aizawa for providing the DT-A vector, J. Miyazaki for the Cre-recombinase expression vector, E. Robertson for the CCE ES cells, H. Sasaki for the Gallus gallus genome, Y. Nakahara and M. Takabe of the Mitsubishi Kagaku Institute of Life Sciences for animal breeding, and S. Ichinose and T. Tajima of Tokyo Medical and Dental University and N. Kawabe and H. Hasegawa of Tokai University for assistance with the in situ hybridization experiments. This work was supported by grants from Research Fellowships of the Japan Society for the Promotion of Science for young Scientists (JSPS) to R.O.; the Asahi Glass Foundation to T.K.-I.; and CREST (the research program of the Japan Science and Technology Agency (JST)), the Uehara Memorial Science Foundation, the Ministry of Health, Labour and Welfare for Child Health and Development (14-C) and the Ministry of Education, Culture, Sports, Science and Technology of Japan to F.I.

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Correspondence to Tomoko Kaneko-Ishino or Fumitoshi Ishino.

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Supplementary information

Supplementary Fig. 1

Placental morphology is normal until 8.5 d.p.c. (PDF 2856 kb)

Supplementary Fig. 2

Fetal-to-placental weight ratios. (PDF 90 kb)

Supplementary Fig. 3

Production of Peg10 loxP KO mice, partial pedigrees of the Peg10 loxP KO mice and the relative expression levels of Peg10 Pat-loxP-KO embryos. (PDF 604 kb)

Supplementary Fig. 4

Peg10 loxP KO embryos show severe growth retardation and placental defects. (PDF 2205 kb)

Supplementary Fig. 5

Rescue of Peg10 Pat-KO embryos by tetraploid wild-type extraembryonic tissues. (PDF 1261 kb)

Supplementary Fig. 6

Expression profile of Ascl2 in Peg10 Pat-KO placentas. (PDF 135 kb)

Supplementary Fig. 7

Comparative genomic analysis of Sgce and Ppp1r9a. (PDF 180 kb)

Supplementary Table 1

Lethality of Peg10 lox-P KO (Pat-lox-P KO) fetuses (PDF 69 kb)

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Ono, R., Nakamura, K., Inoue, K. et al. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nat Genet 38, 101–106 (2006). https://doi.org/10.1038/ng1699

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