How to improve mouse cloning.

The mouse is the most extensively used mammalian laboratory species in biology and medicine because of the ready availability of a wide variety of defined genetic and gene-modified strains and abundant genetic information. Its small size and rapid generation turnover are also advantages compared with other experimental animals. Using these advantages, somatic cell nuclear transfer (SCNT) in mice has provided invaluable information on epigenetics related to SCNT technology and cloning, playing a leading role in relevant technical improvements. These improvements include treatment with histone deacetylase inhibitors, correction of Xist gene expression (controlling X chromosome inactivation), and removal of methylated histones from SCNT-generated embryos, which have proven to be effective for SCNT cloning of other species. However, even with the best combination of these treatments, the birth rate in cloned offspring is still lower than intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). One remaining issue associated with SCNT is placental enlargement (hyperplasia) found in late pregnancy, but this abnormality might not be a major cause for the low efficiency of SCNT because many SCNT-derived embryos die before their placentas start to enlarge at midgestation (early postimplantation stage). It is known that, at this stage, undifferentiated trophoblast cells in the extraembryonic tissue of SCNT-derived embryos fail to proliferate. Understanding the molecular mechanisms is essential for further technical improvements of mouse SCNT, which might also provide clues for technical breakthroughs in mammalian SCNT and cloning in general.