open access

https://hdl.handle.net/2115/68126

Synergistic role of Igf2 and Dlk1 in fetal liver development and hematopoiesis in bi-maternal mice

英語

Mouse

2008-03

日本繁殖生物学会

Journal of Reproduction and Development

54(3)

177-182

Mouse bi-maternal embryos (BMEs) that contain two haploid sets of genomes from non-growing (ng) and fully-grown (fg) oocytes develop to embryonic day (E) 13.5. However, the ng/fg BMEs never develop beyond E13.5 because of repression of the paternally expressed imprinted genes, Igf2 and Dlk1. The present study was conducted to address the issue of whether fetal hematopoietic disorder is involved in the restricted development of BMEs. FACS analysis revealed that the livers of ngwt/fg BMEs contained increased numbers of immature c-kit+/ter119– hematopoietic cells, were while the numbers of mature c-kit–/ter119+ hematopoietic cells were decreased. This finding was supported by histological observations. Quantitative gene expression analysis revealed that Igf2 and Dlk1 expression was repressed in the liver. To understand the role of paternally-methylated imprinted genes on chromosomes 7 and 12, particularly Igf2 and Dlk1, in fetal liver hematopoiesis, we constructed ngΔch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs using ng oocytes harboring deletion of differentially methylated regions at distal chromosomes 7 and/or 12. The ngΔch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs, respectively, express Igf2, Dlk1 and both, and these embryos developed to term with specific phenotypes; the ngΔch7/fg and ngΔch12/fg BMEs develop to term with severe growth retardation, and the ngΔDouble/fg BMEs can survive to become normal female adults. By inducing Igf2 and Dlk1 expression, the proportions of mature and immature hematopoietic cells in the livers of the ngΔch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs were considerably restored, and particularly in the ngΔDouble/fg BMEs, hematopoiesis occurred normally with appropriate expressions of the related genes. These data suggest that inappropriate expression of Igf2 and Dlk1 is involved in impaired fetal hematopoiesis

学術雑誌論文

Version of Record

0916-8818

1348-4400

AA10936678