Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Allele specific inactivation of insulin 1 and 2, in the mouse yolk sac, indicates imprinting

Abstract

Genomic imprinting, gene inactivation during gametogenesis, causes maternal and paternal alleles of some genes to function unequally. We examined the possibility of imprinting in insulin genes because the human insulin gene (ins) and its mouse homologue (ins2) are adjacent to the known imprinted genes, igf2 and H19, and because imprinting has been implicated in the transmission of an ins linked risk for Type I diabetes. We show, by single strand conformational polymorphism (SSCP) analysis of cDNAs from parents and progeny of interspecies mouse crosses, that insulin genes are imprinted. While both alleles of the two mouse insulin genes were active in embryonic pancreas, only paternal alleles for both genes were active in the yolk sac.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Surani, M.A., Barton, S.C. & Norris, M.L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308, 548–550 (1984).

    Article  CAS  PubMed  Google Scholar 

  2. Barlow, D.P., Stoger, R., Germann, B.G., Saito, K. & Schweifer, N. The mouse insulin-like growth factor type 2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84–87 (1991).

    Article  CAS  PubMed  Google Scholar 

  3. Left, S.E. et al. Maternal imprinting of the Snrpn gene and conserved linkage homology with the human Prader willi Syndrome region. Nature Genet. 2, 259–264 (1992).

    Article  Google Scholar 

  4. DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse insulin- like growth factor II gene. Cell 64, 849–859 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Bartolome, M.S., Zemel, S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  Google Scholar 

  6. Rotwein, P. & Hall, L.J. Evolution of insulin-like growth factor ll:characterization of the mouse IGF-II gene and identification of two pseudo-exons. DNA Cell Biol. 9, 725–735 (1990).

    Article  CAS  PubMed  Google Scholar 

  7. O'Malley, K.L. & Rotwein, P. Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11. Nucl. Acids Res. 16, 4437–4446 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Zemel, S., Bartolomei, M.S. & Tilghman, S.M. Physical linkage of two mammalian imprinted genes, H19and insulin-like growth factor 2. Nature Genet. 2, 61–65 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Julier, C. et al. Insulin-IGF2region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent susceptibility. Nature 354, 155–159 (1992).

    Article  Google Scholar 

  10. Soares, M.B. et al. RNA-mediated gene duplication. The rat preproinsulin I gene is a functional retropson. Molec. cell. Biol. 5, 2090–2103 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wentworth, B.M., Schaeffer, I.M., Villa-Komaroff, L. & Chirgwin, J.M. Characterization of the two non-allelic genes encoding mouse preproinsulin. J. molec. Evol. 23, 305–312 (1986).

    Article  CAS  PubMed  Google Scholar 

  12. Lomedico, P. et al. The structure and evolution of the two non-allelic rat preproinsulin genes. cell 18, 545–568 (1979).

    Article  CAS  PubMed  Google Scholar 

  13. Giddings, S.J. & Carnaghi, L. Insulin II gene expression by extraplacental membranes: a non-pancreatic source for fetal insulin. J. biol. Chem. 264, 9462–9469 (1989).

    CAS  PubMed  Google Scholar 

  14. Giddings, S.J. & Carnaghi, L.R. Selective expression and developmental regulation of the ancestral rat insulin II gene in fetal liver. Molec. Endocrinal. 4, 1363–1369 (1990).

    Article  CAS  Google Scholar 

  15. Devaskar, S.U., Singh, B., Rajakumar, P.A., Carnaghi, L.R. & Giddings, S.J. Insulin II gene expression in the central nervous system. Regulatory Peptides 48, 55–63 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Deltour, L. et al. Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo. Proc. natn. Acad. Sci. U.S.A. 90 527–531 (1993).

    Article  CAS  Google Scholar 

  17. Koranyi, L., Permutt, M.A, Chirgwin, J.M. & Giddings, S.J. Proinsulin I and II gene expression in inbred mouse strains. Molec. Endocrinol. 3, 1895–1902 (1989).

    Article  CAS  Google Scholar 

  18. Donohue, D.L. Dysendocrinism. J. Pediatr. 32, 739–748 (1948).

    Article  Google Scholar 

  19. Kadowaki, T. et al. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance J. clin. Invest. 86, 254–264 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Untemnan, T., Goewert-Bauman, G. & Frankel, N. Insulin receptors in embryo and extra-embryonic membranes of the early somite rat conceptus. Diabetes 35, 1193–1199 (1986).

    Article  Google Scholar 

  21. Giddings, S.J. & Carnaghi, L.R. Insulin receptor gene expression during development: developmental regulation of insulin receptor mRNA abundance in embryonic liver and yolk sac, developmental regulation of insulin receptor gene splicing and comparison to abundance of insulin-like growth factor 1 receptor mRNA. Molec. Endocrinol. 6, 1665–1672 (1992).

    CAS  Google Scholar 

  22. Eisen, H.R., Goldfine, I.D. & Glinsman, W.H. Regulation of hepatic glycogen synthesis during fetal development: roles of hydrocortisone, insulin and insulin receptors. Proc. natn. Acad. Sci. U.S.A. 70, 3453–3457 (1973).

    Article  Google Scholar 

  23. Sasaki, H. et al. Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes Dev. 6, 1843–1856 (1992).

    Article  CAS  PubMed  Google Scholar 

  24. Bartholomei, M.S., Webber, A.L., Brunkow, M.E. & Tilghman, S.M. pigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 7, 1663–1673 (1993).

    Article  Google Scholar 

  25. Stoger, R. et al. Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinted signal. Cell 73, 61–71 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Walker, M.D., Edlund, T., Boulet, A.M. & Rutter, W.J. Cell specific expression controlled by the 5′-flanking region of insulin and chymotrypsin genes. Nature 306, 557–561 (1983).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giddings, S., King, C., Harman, K. et al. Allele specific inactivation of insulin 1 and 2, in the mouse yolk sac, indicates imprinting. Nat Genet 6, 310–313 (1994). https://doi.org/10.1038/ng0394-310

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0394-310

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing