Nature 351, 667 - 670 (20 June 1991); doi:10.1038/351667a0

Embryological and molecular investigations of parental imprinting on mouse chromosome 7

A. C. Ferguson-Smith, B. M. Cattanach^*, S. C. Barton, C. V. Beechey^* & M. A. Surani

Department of Molecular Embryology, AFRC Institute of Animal Physiology 6 Genetics Research, Babraham, Cambridge CB2 4AT, UK
^*MRC Radiobiology Unit, Chilton, Didcot, Oxford 0X1 ORD, UK

MOUSE embryos with duplications of whole maternal (partheno-genetic and gynogenetic) or paternal (androgenetic) genomes show reciprocal phenotypes and do not develop to term^1,2. Genetic complementation has identified the distal region of chromosome 7 (Chr 7) as one of the regions for which both a maternal and paternal chromosome copy are essential for normal development, presumably because of the presence of imprinted genes whose expression is dependent on their parental origin^3,4. Embryos with the maternal duplication and paternal deficiency of distal Chr 7 are growth retarded and die around day 16 of gestation; the reciprocal paternal duplication embryos die at an unidentified earlier stage⁴. We report here the incorporation of cells with the paternal duplication into chimaeras, resulting in a striking growth enhancement of the embryos. One gene located on mouse distal Chr 7 (ref. 5) is the insulin-like growth factor 2 (Igf2) gene, an embryonic mitogen⁶. In embryos with the maternal duplication of distal Chr 7, the two maternal alleles of the Igf2 gene are repressed. The presence of two paternal alleles of this gene in many cells is probably responsible for the growth enhancement observed in chimaeras. We propose that there are other imprinted genes in this Chr 7 region. We also compare the imprinting of this sub-genomic region with phenotypes resulting from the duplication of the whole parental genome in parthenogenones and androgenones.

References

1.	Surani, M. A. H. in Experimental Approaches to Mammalian Embryonic Development (ed. Rossant, J. & Pedersen, R. A.) 401−435. (Cambridge University Press, Cambridge, 1986).
2.	Solter, D. A. Rev. Genet. 22, 127−146 (1988). | Article | ISI | ChemPort |
3.	Cattanach, B. M. J. Embryol. exp. Morph. 97, 137−150 (1986). | PubMed |
4.	Searle, A. G. & Beechey, C. V. Genet. Res. 56, 237−244 (1990). | PubMed | ISI | ChemPort |
5.	Rotwein, P. & Hall, L. DNA Cell Biol. 9, 725−735 (1990). | PubMed | ISI | ChemPort |
6.	Beck, F. et al. Development 101, 175−184 (1987). | PubMed | ChemPort |
7.	Lyon, M. F. & Searle, A. G. Genetic Variants and Strains of the Laboratory Mouse 2nd edn 592 (Oxford University Press, Oxford, 1989).
8.	Searle, A. G., Ford, C. E. & Beechey, C. V. Genet. Res. 18, 215−235 (1971). | PubMed | ChemPort |
9.	Lee, J., Pintar, J. & Efstratiadis, A. Development 110, 151−159 (1990). | PubMed | ISI | ChemPort |
10.	De Chiara, T. M., Robertson, E. J. & Efstratiadis, A. Cell 64, 849−860 (1991). | Article | PubMed | ISI | ChemPort |
11.	Barlow, D. P., Stoger, R., Herrmann, B. G., Saito, K. & Schweifer, N. Nature 349, 84−87 (1991). | Article | PubMed | ISI | ChemPort |
12.	Surani, M. A. et al. Development Suppl. 89−98 (1990).
13.	Fundele, R. et al. Development 108, 203−211 (1990). | PubMed | ISI | ChemPort |
14.	Stylianopoulou, F. et al. Development 103, 497−506 (1988). | PubMed | ChemPort |
15.	Mann, J. R., Gadi, I., Harbison, M. L., Abbondanzo, S. J. & Stewart, C. L. Cell 62, 251−260 (1990). | Article | PubMed | ISI | ChemPort |
16.	Fundele, R., Norris, M., Barton, S. C., Reik, W. & Surani, M. A. Development 106, 28−35 (1989).
17.	De Chiara, T. M., Efstratiadis, A. & Robertson, E. J. Nature 345, 78−80 (1990). | Article | PubMed | ISI | ChemPort |
18.	Reik, W. Trends Genet. 5, 331−336 (1989). | Article | PubMed | ISI | ChemPort |
19.	Hall, J. Am. J. hum. Genet. 46, 857−873 (1990). | PubMed | ISI | ChemPort |
20.	Ferguson-Smith, A. C., Reik, W. & Surani, M. A. Cancer Surveys 9, 487−503 (1990). | PubMed | ChemPort |
21.	Ohlsson, R., Holmgren, L., Glaser, A., Szpecht, A. & Pfeifer-Ohlsson, S. EMBO J. 8, 1993−1999 (1989). | PubMed | ISI | ChemPort |
22.	Nicholls, R. et al. Am. J. hum. Genet. 46, A230 (1990).
23.	Barton, S. C., Adams, C. A., Norris, M. L. & Surani, M. A. H. J. Embryol. exp. Morph. 90, 267−285 (1985). | PubMed | ChemPort |
24.	Solter, D. & Knowles, B. Proc. natn. Acad. Sci. U.S.A. 72, 5099−5102 (1975). | ChemPort |
25.	Babinet, C. Expl Cell Res. 130, 15−19 (1980). | ChemPort |
26.	Gardner, R. L. in Methods in Mammalian Reproduction (ed. Daniel, J. C. Jr) 137−165 (Academic Press, New York, New York, 1978).
27.	Winking, H. & Silver, L. M. Genetics 108, 1013−1020 (1984). | PubMed | ISI | ChemPort |
28.	Chomcynski, P. & Sacchi, N. Ann. Biochem. 162, 156−159 (1987). | Article | ChemPort |
29.	Maniatis, T., Fritsch, E. F. & Sambrook, J. Moleular Cloning: a Laboratory Manual (CSH, USA, 1982).
30.	Bartolomei, M. S., Zemel, S. & Tilghman, S. M. Nature 351, 153−155 (1991). | Article | PubMed | ISI | ChemPort |