Abstract
Nkx2.2 is a homeobox transcription factor that is expressed in the pancreas, intestine and central nervous system (CNS) during embryogenesis and in the adult. In mice, global deletion of Nkx2.2 results in cell mis-specification in each of the tissues where it is expressed, and the null mice die as neonates with severe hyperglycemia. Although a whole body knockout demonstrates the importance of Nkx2.2 in cell specification and postnatal viability, it precludes assessment of the cell-autonomous and postnatal functions of Nkx2.2. In this study we report the generation and functional characterization of mice encoding a conditional allele of Nkx2.2. We demonstrate the functional integrity of the conditional Nkx2.2 allele and report successful in vivo deletion using a pancreas-specific Cre recombinase. The pancreas-specific deletion of Nkx2.2 results in similar defects found in the Nkx2.2 null pancreas and the mice die shortly after birth, demonstrating that the neonatal lethality associated with the null allele is caused by pancreatic islet dysfunction. The generation of a conditional Nkx2.2 allele provides an important tool for identifying the cell-autonomous and postnatal activities of Nkx2.2 in establishing and maintaining cell type identities and functions in the pancreas, intestine and CNS.
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Acknowledgments
The authors acknowledge the previous efforts of Dr. Lei Zhang and Aimee Bernard in their attempts to generate a conditional allele of Nkx2.2. Support for this study was provided by National Institutes of Health (NIH) Beta Cell Biology Consortium (BCBC) grants U01 DK072504 and U01 DK089523 (LS); NIH grant R01 DK082590 (LS); Naomi Berrie Fellowship in Diabetes Research and Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship (TLM). Additional support was provided by the Columbia University DERC (P30 DK63608), the Columbia Cancer Center Transgenic Mouse/ES Cell Core Facility, and Precision Targeting Lab, LLC.
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Mastracci, T.L., Lin, CS. & Sussel, L. Generation of mice encoding a conditional allele of Nkx2.2 . Transgenic Res 22, 965–972 (2013). https://doi.org/10.1007/s11248-013-9700-0
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DOI: https://doi.org/10.1007/s11248-013-9700-0