Rats have important advantages over mice as an experimental system for physiological and pharmacological investigations. The lack of rat embryonic stem (ES) cells has restricted the availability of transgenic technologies to create genetic models in this species. Here, we show that rat ES cells can be efficiently derived, propagated, and genetically manipulated in the presence of small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. These rat ES cells express pluripotency markers and retain the capacity to differentiate into derivatives of all three germ layers. Most importantly, they can produce high rates of chimerism when reintroduced into early stage embryos and can transmit through the germline. Establishment of authentic rat ES cells will make possible sophisticated genetic manipulation to create models for the study of human diseases.
[1]Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA.
[2]Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[3]Univ So Calif, Keck Sch Med, Custom Microarray Core Facil, Inst Med Genet, Los Angeles, CA 90033 USA.
[4]Univ So Calif, Keck Sch Med, Knockout Core Facil, Norris Canc Ctr Transgen, Los Angeles, CA 90033 USA.
[5]Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA.
[6]Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Urol, Los Angeles, CA 90033 USA.
[7]Fudan Univ, Shanghai Med Coll, Minist Educ, Key Lab Mol Med, Shanghai 20032, Peoples R China.
(8.0+极速模式)