دورية أكاديمية
أعرض في EDS

Deletion of Pax1 scoliosis-associated regulatory elements leads to a female-biased tail abnormality.

التفاصيل البيبلوغرافية
العنوان: Deletion of Pax1 scoliosis-associated regulatory elements leads to a female-biased tail abnormality.
المؤلفون: Ushiki A; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Sheng RR; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Zhang Y; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China., Zhao J; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Nobuhara M; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Murray E; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Ruan X; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA., Rios JJ; Center for Translational Research, Scottish Rite for Children, Dallas, TX 75390, USA; Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Wise CA; Center for Translational Research, Scottish Rite for Children, Dallas, TX 75390, USA; Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Ahituv N; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: nadav.ahituv@ucsf.edu.
المصدر: Cell reports [Cell Rep] 2024 Mar 26; Vol. 43 (3), pp. 113907. Date of Electronic Publication: 2024 Mar 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Scoliosis*/genetics , Scoliosis*/epidemiology, Animals ; Female ; Mice ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Tail ; Transcription Factors/genetics
مستخلص: Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is sexually dimorphic, with increased incidence in females. A genome-wide association study identified a female-specific AIS susceptibility locus near the PAX1 gene. Here, we use mouse enhancer assays, three mouse enhancer knockouts, and subsequent phenotypic analyses to characterize this region. Using mouse enhancer assays, we characterize a sequence, PEC7, which overlaps the AIS-associated variant, and find it to be active in the tail tip and intervertebral disc. Removal of PEC7 or Xe1, a known sclerotome enhancer nearby, or deletion of both sequences lead to a kinky tail phenotype only in the Xe1 and combined (Xe1+PEC7) knockouts, with only the latter showing a female sex dimorphic phenotype. Extensive phenotypic characterization of these mouse lines implicates several differentially expressed genes and estrogen signaling in the sex dimorphic bias. In summary, our work functionally characterizes an AIS-associated locus and dissects the mechanism for its sexual dimorphism.
Competing Interests: Declaration of interests N.A. is a co-founder and on the scientific advisory board of Regel Therapeutics. N.A. receives funding from BioMarin Pharmaceutical Incorporated.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
التعليقات: Update of: bioRxiv. 2023 Apr 13;:. (PMID: 37090618)
References: Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):. (PMID: 33850013)
N Engl J Med. 2013 Oct 17;369(16):1512-21. (PMID: 24047455)
Front Cell Dev Biol. 2020 Nov 04;8:582255. (PMID: 33251213)
Cell Cycle. 2014;13(9):1400-12. (PMID: 24626186)
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8692-7. (PMID: 9671740)
Science. 2020 Sep 11;369(6509):. (PMID: 32913072)
Nucleic Acids Res. 2006 Jun 06;34(10):3150-60. (PMID: 16757580)
Front Mol Neurosci. 2022 Aug 02;15:958568. (PMID: 35983069)
Biol Open. 2017 Feb 15;6(2):187-199. (PMID: 28011632)
Nature. 2018 Feb 8;554(7691):239-243. (PMID: 29420474)
Hum Mol Genet. 2022 Jul 7;31(13):2279-2293. (PMID: 35022708)
Nat Genet. 2008 Nov;40(11):1279-81. (PMID: 18849994)
Development. 2005 Feb;132(4):787-96. (PMID: 15677726)
J Med Genet. 2014 Jun;51(6):401-6. (PMID: 24721834)
Eur Spine J. 2012 Jun;21(6):1069-74. (PMID: 22094388)
Hum Mol Genet. 2018 Nov 15;27(22):3986-3998. (PMID: 30395268)
PLoS One. 2014 Jan 24;9(1):e87018. (PMID: 24475213)
Cytogenet Genome Res. 2005;111(1):16-26. (PMID: 16093716)
Nat Genet. 2008 Dec;40(12):1445-53. (PMID: 19011630)
Development. 1996 Jan;122(1):23-30. (PMID: 8565834)
Nucleic Acids Res. 2020 Jan 8;48(D1):D87-D92. (PMID: 31701148)
Genetics. 1937 Jan;22(1):1-13. (PMID: 17246824)
Am J Hum Genet. 2011 Jun 10;88(6):819-826. (PMID: 21636067)
Am J Hum Genet. 2015 Aug 6;97(2):337-42. (PMID: 26211971)
Nat Genet. 2009 Aug;41(8):946-52. (PMID: 19633672)
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1241-1247. (PMID: 30945573)
Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651)
Nature. 1988 Sep 29;335(6189):435-7. (PMID: 3138544)
Dev Biol. 2022 Feb;482:82-90. (PMID: 34915022)
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2538-43. (PMID: 12601169)
Exp Mol Med. 2018 Nov 7;50(11):1-11. (PMID: 30405118)
Nat Commun. 2015 Mar 18;6:6452. (PMID: 25784220)
Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
Bone Res. 2020 Mar 9;8:13. (PMID: 32195011)
Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2208623119. (PMID: 36584300)
J Bone Joint Surg Am. 1993 Dec;75(12):1804-10. (PMID: 8258551)
Methods Mol Biol. 2006;326:103-13. (PMID: 16780196)
Dev Cell. 2017 Aug 21;42(4):388-399.e3. (PMID: 28829946)
Nature. 2012 Sep 6;489(7414):57-74. (PMID: 22955616)
Eur Spine J. 2014 Feb;23(2):455-62. (PMID: 24136418)
Sci Rep. 2019 Mar 14;9(1):4605. (PMID: 30872687)
Nat Commun. 2015 Sep 22;6:8355. (PMID: 26394188)
Orthop Clin North Am. 2006 Oct;37(4):555-8. (PMID: 17141012)
Am J Hum Genet. 2002 Aug;71(2):401-6. (PMID: 12094330)
Nature. 2009 May 7;459(7243):108-12. (PMID: 19295514)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Hum Mol Genet. 2011 Apr 1;20(7):1456-66. (PMID: 21216876)
Annu Rev Genomics Hum Genet. 2017 Aug 31;18:45-63. (PMID: 28399667)
Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144B(3):388-90. (PMID: 17171652)
Biomed Pharmacother. 2018 Oct;106:1220-1226. (PMID: 30119190)
PLoS One. 2013 Sep 04;8(9):e72802. (PMID: 24023777)
Nat Genet. 2011 Oct 23;43(12):1237-40. (PMID: 22019779)
Nat Genet. 2005 Oct;37(10):1035-7. (PMID: 16155570)
J Mol Endocrinol. 2017 Nov;59(4):351-363. (PMID: 28871061)
Eur Spine J. 2013 Mar;22 Suppl 2:S81-95. (PMID: 23099524)
Nat Commun. 2019 Aug 15;10(1):3685. (PMID: 31417091)
Nat Genet. 2008 Nov;40(11):1282-4. (PMID: 18849991)
Nat Genet. 2013 Jun;45(6):676-9. (PMID: 23666238)
Nucleic Acids Res. 2022 Jan 7;50(D1):D988-D995. (PMID: 34791404)
Nat Genet. 2008 Dec;40(12):1454-60. (PMID: 19011629)
Development. 2021 Oct 15;148(20):. (PMID: 34679163)
Development. 1999 Dec;126(23):5399-408. (PMID: 10556064)
Science. 2008 Sep 5;321(5894):1314. (PMID: 18772429)
Cell. 2018 Jan 25;172(3):491-499.e15. (PMID: 29358049)
Science. 2016 Jun 10;352(6291):1341-4. (PMID: 27284198)
Genesis. 2013 Jun;51(6):420-9. (PMID: 23377878)
Dev Biol. 2018 Mar 1;435(1):84-95. (PMID: 29355522)
Development. 1994 May;120(5):1109-21. (PMID: 8026324)
Cell Rep. 2020 Oct 27;33(4):108311. (PMID: 33113369)
Hum Mol Genet. 2021 Jan 21;29(22):3606-3615. (PMID: 33179741)
Science. 2007 Apr 13;316(5822):285-8. (PMID: 17431181)
Commun Biol. 2019 Jun 20;2:226. (PMID: 31240264)
Biomed Res. 2013 Jun;34(3):119-28. (PMID: 23782745)
معلومات مُعتمدة: P01 HD084387 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: AIS; CP: Molecular biology; GWAS; Pax1; enhancer; scoliosis; sexual dimorphism
المشرفين على المادة: 0 (Transcription Factors)
142661-96-9 (PAX1 transcription factor)
تواريخ الأحداث: Date Created: 20240310 Date Completed: 20240401 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC11005513
DOI: 10.1016/j.celrep.2024.113907
PMID: 38461417
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2024.113907