Knock-out rat production and organ regeneration using embryonic stem cells

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The ultimate objective of the present study is to produce gene-modified rats useful for regenerative medical research using pluripotent embryonic stem cells (ESCs) and advanced reproductive technologies (ART). Rats expressing the kusabira-orange gene, as well as rats expressing the tdTomato gene knock-in at Rosa26 locus, were successfully produced in preliminary trials. Rats lacking Pdx1 gene were also produced by a similar ART protocol with ESCs (Pdx1-deficient mice have no pancreas), but these rats did not show any phenotypic loss of the pancreas. However, functional rat pancreas was successfully regenerated in adult mice by injecting rat wild-type pluripotent stem cells (PSCs) into Pdx1/KO mouse blastocysts.