Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons

Ling Li, Lin Gao, Kejia Wang, Xianhua Ma, Xusheng Chang, Jian Hui Shi, Ye Zhang, Kai Yin, Zhimin Liu, Yuguang Shi, Zhifang Xie, Weiping J. Zhang

Research output: Contribution to journalArticle

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Abstract

The recombination efficiency and cell specificity of Cre driver lines are critical for exploring pancreatic β cell biology with the Cre/LoxP approach. Some commonly used Cre lines are based on the short Ins2 promoter fragment and show recombination activity in hypothalamic neurons; however, whether this stems from endogenous Ins2 promoter activity remains controversial. In this study, we generated Ins2-Cre knockin mice with a targeted insertion of IRES-Cre at the Ins2 locus and demonstrated with a cell lineage tracing study that the Ins2 gene is not transcriptionally active in the hypothalamus. The Ins2-Cre driver line displayed robust Cre expression and activity in pancreatic β cells without significant alterations in insulin expression. In the brain, Cre activity was mainly restricted to the choroid plexus, without significant recombination detected in the hippocampus or hypothalamus by the LacZ or fluorescent tdTomato reporters. Furthermore, Ins2-Cre mice exhibited normal glucose tolerance and insulin secretion upon glucose stimulation in vivo. In conclusion, this Ins2-Cre driver line allowed high-fidelity detection of endogenous Ins2 promoter activity in vivo, and the negative activity in the hypothalamus demonstrated that this system is a promising alternative tool for studying β cell biology.

Original languageEnglish (US)
Article number20438
JournalScientific Reports
Volume6
DOIs
StatePublished - Feb 2 2016

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Genetic Recombination
Hypothalamus
Neurons
Cell Biology
Insulin
Genes
Glucose
Choroid Plexus
Cell Lineage
Hippocampus
Brain

ASJC Scopus subject areas

  • General

Cite this

Li, L., Gao, L., Wang, K., Ma, X., Chang, X., Shi, J. H., ... Zhang, W. J. (2016). Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons. Scientific Reports, 6, [20438]. https://doi.org/10.1038/srep20438

Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons. / Li, Ling; Gao, Lin; Wang, Kejia; Ma, Xianhua; Chang, Xusheng; Shi, Jian Hui; Zhang, Ye; Yin, Kai; Liu, Zhimin; Shi, Yuguang; Xie, Zhifang; Zhang, Weiping J.

In: Scientific Reports, Vol. 6, 20438, 02.02.2016.

Research output: Contribution to journalArticle

Li, L, Gao, L, Wang, K, Ma, X, Chang, X, Shi, JH, Zhang, Y, Yin, K, Liu, Z, Shi, Y, Xie, Z & Zhang, WJ 2016, 'Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons', Scientific Reports, vol. 6, 20438. https://doi.org/10.1038/srep20438
Li, Ling ; Gao, Lin ; Wang, Kejia ; Ma, Xianhua ; Chang, Xusheng ; Shi, Jian Hui ; Zhang, Ye ; Yin, Kai ; Liu, Zhimin ; Shi, Yuguang ; Xie, Zhifang ; Zhang, Weiping J. / Knockin of Cre Gene at Ins2 Locus Reveals No Cre Activity in Mouse Hypothalamic Neurons. In: Scientific Reports. 2016 ; Vol. 6.
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