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Sci Rep. 2018 Dec 5;8(1):17642. doi: 10.1038/s41598-018-36097-6.

Generation of a highly efficient and tissue-specific tryptophan hydroxylase 1 knockout mouse model.

Author information

1
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
2
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
3
Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA.
4
Center for Bioanalysis, Division of Chemical and Medical Metrology, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea. jsjeong@kriss.re.kr.
5
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea. hailkim@kaist.edu.
6
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea. hailkim@kaist.edu.

Abstract

Recent studies on tissue-autonomous serotonin (5-hydroxytryptamine [5-HT]) function have identified new roles for 5-HT in peripheral organs. Most of these studies were performed by crossing mice carrying the Tph1tm1Kry allele with tissue specific Cre mice. In the present study, we found that 5-HT production was not completely abolished in Tph1tm1Kry KO mice. The residual 5-HT production in Tph1tm1Kry KO mice is attributed to the expression of a truncated form of TPH1 containing the catalytic domain. Hence, in an effort to obtain mice with a Tph1 null phenotype, we generated mice harboring a new Tph1 floxed allele, Tph1tm1c, targeting exons 5 and 6 which encode the catalytic domain of TPH1. By crossing the new Tph1 floxed mice with villin-Cre or insulin-Cre mice, we observed near-complete ablation of 5-HT production in the intestine and β cells. In conclusion, this improved Tph1 floxed mouse model will serve as useful and accurate tool for analyzing peripheral 5-HT system.

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