An allelic series for the leptin receptor gene generated by CRE and FLP recombinase

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Julie E McMinnStreamson C Chua

Abstract

Body weight regulation is mediated through several major signaling pathways, some of which have been delineated by positional cloning of spontaneous genetic mutations in mice. Lepr(db/db) mice are obese due to a defect in the signaling portion of the leptin receptor, which has led to extensive study of this highly conserved system over the past several years. We have created an allelic series at Lepr for the further examination of LEPR signaling phenotypes using both the FLP /frt and CRE /loxP systems. By inserting a frt-PGK-neo-frt sequence in Lepr intron 16, we have generated a conditional gene repair Lepr allele ( Lepr-neo) that elicits morbid obesity, diabetes, and infertility in homozygous mice, recapitulating the obesity syndrome of Lepr(db/db) mice. Thus, in vivo excision of the PGK-neo cassette with a FLP recombinase transgene restores the lean and fertile phenotype to Lepr(flox/flox) mice. In the same construct, we have also inserted loxP sites that flank Lepr coding exon 17, a region that encodes a JAK docking site required for STAT3 signaling. CRE-mediated excision of Lepr coding exon 17 from Lepr with a frameshift in subsequent exons results in a syndrome of obesity, diabetes, and infertility in LeprDelta17/Delta17 ...Continue Reading

References

Feb 22, 1978·Pflügers Archiv : European journal of physiology·P Trayhurn, W P James
Jan 1, 1982·Diabetes·D L Coleman
Jul 28, 1995·Science·M A PelleymounterF Collins
Sep 1, 1994·Molecular and Cellular Biology·J ChengL E Maquat
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·S M Dymecki
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·N GhilardiR C Skoda
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·J L HalaasJ M Friedman
Feb 9, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·J A BrownJ G Vandenbergh
Mar 21, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·P DietrichA Efstratiadis
Feb 13, 2001·Nucleic Acids Research·I Dragatsis, S Zeitlin
Oct 17, 2001·The Journal of Clinical Investigation·P CohenJ M Friedman

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Citations

Dec 30, 2011·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·E L SchellerP H Krebsbach
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yu ShiGerard Karsenty
May 11, 2011·Cells, Tissues, Organs·Erica L SchellerPaul H Krebsbach
Nov 15, 2005·The Journal of Clinical Investigation·Carl de LucaStreamson C Chua
Oct 3, 2007·The Journal of Clinical Investigation·Kevin D Niswender, Mark A Magnuson
Oct 25, 2012·Journal of Lipid Research·Rok KeberSimon Horvat
Jan 31, 2009·Endocrinology·Janette H QuennellGreg M Anderson
Nov 19, 2010·Endocrinology·Gwen V ChildsRhonda D Kineman
Jan 19, 2013·Journal of Applied Physiology·Bhavaani JayaramAbba J Kastin
Jul 14, 2011·Journal of Cellular Biochemistry·Erica L SchellerPaul H Krebsbach
Oct 7, 2015·The International Journal of Neuropsychopharmacology·Jing LiuXin-Yun Lu
Oct 27, 2015·Molecular Metabolism·Amanda LaqueHeike Münzberg
Jun 11, 2015·Immunology·Jayasree SreenivasanAdrian Liston
Aug 7, 2013·Brain, Behavior, and Immunity·Pramod K MishraWeihong Pan
Apr 22, 2014·Hormones and Behavior·Nicole Bellefontaine, Carol F Elias
Apr 2, 2015·Molecular Metabolism·Margaret B AllisonDavid P Olson
Feb 18, 2015·Journal of Molecular Neuroscience : MN·Yuping WangWeihong Pan
Aug 31, 2012·The International Journal of Neuropsychopharmacology·Ming GuoXin-Yun Lu
May 5, 2005·American Journal of Physiology. Endocrinology and Metabolism·Julie E McMinnStreamson C Chua

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