title: Generation of mice encoding a conditional null allele of Gcm2.
abstract: Glial cells missing homolog 2 (GCM2) is a transcription factor that is expressed predominately in the pharyngeal pouches and, at later stages, in the developing and mature parathyroid glands. In humans, loss of GCM2 function, either through recessive apomorphic mutations or dominant inhibitor mutations in the human GCM2 gene, leads to isolated hypoparathyroidism. In mice, homozygous disruption of Gcm2 by conventional gene targeting results in parathyroid aplasia and hypoparathyroidism. In this study, we report the generation and functional characterization of mice encoding a conditional null allele of Gcm2. We demonstrate the functional integrity of the conditional Gcm2 allele and report successful in vivo deletion of exon 2 using Cre recombinase. The mice with conditional deletion of Gcm2 displayed phenotypes similar to those previously described for a conventional Gcm2 knockout, including perinatal lethality, hypocalemia, low or undetectable serum levels of parathyroid hormone, and absent parathyroid glands. The production of a conditional mutant allele for Gcm2 represents a valuable resource for the study of the temporal- and spatial-specific roles for Gcm2, and for understanding the postnatal activities of GCM2 protein.
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, 10461, USA.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Yuan
authors.forename: Evan E
authors.initials: EE
authors.lastname: Opas
authors.forename: Chakravarthy
authors.initials: C
authors.lastname: Vrikshajanani
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology*; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000378:metabolism*; D010641:Phenotype; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C523486:Gcm2 protein, mouse; D009687:Nuclear Proteins; D010281:Parathyroid Hormone; D014157:Transcription Factors; C045073:Cre recombinase; D019426:Integrases
references.citation: J Med Genet. 2005 May;42(5):443-8
references.pmid: 15863676
references.citation: Cell. 1995 Sep 22;82(6):1013-23
references.pmid: 7553843
references.citation: Med Hypotheses. 2006;67(3):482-7
references.pmid: 16697534
references.citation: Dev Biol. 2007 May 1;305(1):333-46
references.pmid: 17382312
references.citation: Am J Physiol Endocrinol Metab. 2013 Feb 1;304(3):E310-20
references.pmid: 23233539
references.citation: Nucleic Acids Res. 1998 May 15;26(10):2337-43
references.pmid: 9580683
references.citation: Endocrinology. 1995 Dec;136(12):5600-7
references.pmid: 7588314
references.citation: Endocrinology. 1990 Nov;127(5):2517-22
references.pmid: 2226330
references.citation: Curr Opin Nephrol Hypertens. 2008 Jul;17(4):353-6
references.pmid: 18660669
references.citation: Science. 1997 Aug 22;277(5329):1025
references.pmid: 9289845
references.citation: J Clin Endocrinol Metab. 2004 Jan;89(1):8-12
references.pmid: 14715818
references.citation: PLoS Genet. 2010 Dec 23;6(12):e1001251
references.pmid: 21203493
references.citation: Mech Dev. 2001 May;103(1-2):141-3
references.pmid: 11335122
references.citation: Adv Exp Med Biol. 2012;728:92-9
references.pmid: 22396164
references.citation: J Bone Miner Res. 2005 Nov;20(11):1944-50
references.pmid: 16234967
references.citation: Endocr J. 2007 Jun;54(3):465-70
references.pmid: 17464094
references.citation: J Cell Biol. 2004 Sep 13;166(6):765-8
references.pmid: 15353544
references.citation: J Clin Endocrinol Metab. 2005 May;90(5):2487-92
references.pmid: 15728199
references.citation: J Pediatr Endocrinol Metab. 2012;25(7-8):741-6
references.pmid: 23155703
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12364-9
references.pmid: 9770492
references.citation: J Bone Miner Res. 2010 Mar;25(3):594-605
references.pmid: 19968565
references.citation: J Clin Invest. 2001 Oct;108(8):1215-20
references.pmid: 11602629
references.citation: J Clin Endocrinol Metab. 2010 Jul;95(7):3512-6
references.pmid: 20463099
references.citation: J Bone Miner Res. 2014 Mar;29(3):693-704
references.pmid: 24038141
references.citation: FEBS Lett. 2002 Sep 25;528(1-3):95-100
references.pmid: 12297286
references.citation: Cell. 1995 Sep 22;82(6):1025-36
references.pmid: 7553844
references.citation: J Bone Miner Res. 2011 Oct;26(10):2463-72
references.pmid: 21713993
references.citation: EMBO J. 2003 Apr 15;22(8):1835-45
references.pmid: 12682016
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14912-6
references.pmid: 8962155
references.citation: J Clin Endocrinol Metab. 2008 Apr;93(4):1426-32
references.pmid: 18182452
references.citation: Nature. 2000 Jul 13;406(6792):199-203
references.pmid: 10910362
references.citation: Nat Neurosci. 2011 Jul 17;14(8):957-64
references.pmid: 21765423
references.citation: Hum Mutat. 2009 Jan;30(1):85-92
references.pmid: 18712808
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14602-7
references.pmid: 9405659
references.citation: J Clin Invest. 2010 Jun;120(6):2144-55
references.pmid: 20484821
references.citation: FEBS Lett. 1996 Sep 16;393(2-3):201-4
references.pmid: 8814290
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17716-9
references.pmid: 15591343
references.citation: Trends Genet. 2001 May;17(5):286-90
references.pmid: 11335039
references.citation: J Clin Endocrinol Metab. 2008 Sep;93(9):3568-76
references.pmid: 18583467
references.citation: Endocrinology. 2005 Nov;146(11):4697-709
references.pmid: 16099856
references.citation: J Clin Endocrinol Metab. 2004 Sep;89(9):4489-92
references.pmid: 15356053
references.citation: Neuron. 2005 Oct 20;48(2):237-51
references.pmid: 16242405
references.citation: Cytogenet Cell Genet. 1999;84(1-2):43-7
references.pmid: 10343099