Editing Chimera (genetics) (section)

====Underlying biology====
The ability to make mouse chimeras comes from an understanding of early mouse development. Between the stages of fertilization of the egg and the implantation of a blastocyst into the uterus, different parts of the mouse embryo retain the ability to give rise to a variety of cell lineages. Once the embryo has reached the blastocyst stage, it is composed of several parts, mainly the [[trophectoderm]], the [[inner cell mass]], and the [[primitive endoderm]]. Each of these parts of the blastocyst gives rise to different parts of the embryo; the inner cell mass gives rise to the embryo proper, while the trophectoderm and primitive endoderm give rise to extra embryonic structures that support growth of the embryo.<ref>{{cite journal | doi = 10.1111/j.1399-0004.2005.00478.x | pmid = 15996204 | last1 = Ralston | first1 = A | last2 = Rossant | first2 = J | year = 2005 | title = Genetic regulation of stem cell origins in the mouse embryo | journal = Clin Genet | volume = 68 | issue = 2| pages = 106–112| s2cid = 25979571 }}</ref> Two- to eight-cell-stage embryos are competent for making chimeras, since at these stages of development, the cells in the embryos are not yet committed to give rise to any particular cell lineage, and could give rise to the inner cell mass or the trophectoderm. In the case where two diploid eight-cell-stage embryos are used to make a chimera, chimerism can be later found in the [[epiblast]], primitive [[endoderm]], and trophectoderm of the mouse [[blastocyst]].<ref>{{cite journal | doi = 10.1242/dev.00893 | last1 = Tam | first1 = P.L. | last2 = Rossant | first2 = J. | year = 2003 | title = Mouse embryonic chimeras: tools for studying mammalian development | journal = Development | volume = 130 | issue = 25| pages = 6155–6163 | pmid = 14623817 | doi-access = | s2cid = 17534775 }}</ref><ref>{{cite journal | last1 = Rossant | first1 = J. | year = 1976 | title = Postimplantation development of blastomeres isolated from 4- and 8-cell mouse eggs | journal = J. Embryol. Exp. Morphol. | volume = 36 | issue = 2| pages = 283–290 | pmid = 1033982}}</ref>

It is possible to dissect the embryo at other stages so as to accordingly give rise to one lineage of cells from an embryo selectively and not the other. For example, subsets of blastomeres can be used to give rise to chimera with specified cell lineage from one embryo. The Inner Cell Mass of a diploid blastocyst, for example, can be used to make a chimera with another blastocyst of eight-cell diploid embryo; the cells taken from the inner cell mass will give rise to the primitive endoderm and to the epiblast in the chimera mouse.<ref>{{Cite journal |last1=Pappaioannou |first1=V. |first2=R. |last2=Johnson |year=1993 |title=Production of chimeras and genetically defined offspring from targeted ES cells |journal=Gene Targeting: A Practical Approach |editor-last=Joyner |editor-first=A. |publisher=IRL Press at [[Oxford University Press]] |pages=107–146}}</ref>
From this knowledge, [[ES cell]] contributions to chimeras have been developed. ES cells can be used in combination with eight-cell-and two-cell-stage embryos to make chimeras and exclusively give rise to the embryo proper. Embryos that are to be used in chimeras can be further genetically altered to specifically contribute to only one part of chimera. An example is the chimera built off of ES cells and tetraploid embryos, which are artificially made by electrofusion of two two-cell diploid embryos. The tetraploid embryo will exclusively give rise to the trophectoderm and primitive endoderm in the chimera.<ref>{{cite journal | doi = 10.1016/0014-4827(85)90143-0 | last1 = Kubiak | first1 = J | last2 = Tarkowski | first2 = A. | year = 1985 | title = Electrofusion of mouse blastomeres. Exp | journal = Cell Res. | volume = 157 | issue = 2| pages = 561–566 | pmid=3884349}}</ref><ref>{{Cite journal |last1=Nagy |first1=A. |first2=J. |last2=Rossant |year=1999 |title=Production of Es-cell aggregation chimeras |journal=Gene Targeting: A Practical Approach |editor-last=Joyner |editor-first=A. |publisher=IRL Press at [[Oxford University Press]] |pages=107–205}}</ref>