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


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.

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  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 5

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

  6. 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).

  7. 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).

  8. 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).

  9. 9

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

  10. 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).

  11. 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).

  12. 12

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

  13. 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).

  14. 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).

  15. 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).

  16. 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).

  17. 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).

  18. 18

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

  19. 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).

  20. 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).

  21. 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).

  22. 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).

  23. 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).

  24. 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).

  25. 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).

  26. 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).

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