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ENDOTHELIAL NEUROPILIN DISRUPTION IN MICE CAUSES DIGEORGE SYNDROME-LIKE MALFORMATIONS INDEPENDENT OF TBX1
by
Jingjing Zhou
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partially Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(GENETIC, MOLECULAR, AND CELLULAR BIOLOGY)
August 2011
Copyright 2011 Jingjing Zhou
Object Description
| Title | Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like malformations independent of Tbx1 |
| Author | Zhou, Jingjing |
| Author email | ustczjj@hotmail.com;jingjinz@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Genetic, Molecular and Cellular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-05-24 |
| Date submitted | 2011-06-30 |
| Date approved | 2011-06-30 |
| Restricted until | 2011-06-30 |
| Date published | 2011-06-30 |
| Advisor (committee chair) | Sucov, Henry |
| Advisor (committee member) |
Chai, Yang Ma, Le |
| Abstract | DiGeorge syndrome is a spectrum of congenital malformations including craniofacial defects, thymus and thyroid/parathyroid hypoplasia, interrupted aortic arch, ventricle septation defects, and outflow tract malformations such as persistent truncus arteriosus and Tetralogy of Fallot. In humans, DiGeorge syndrome is usually caused by heterozygous deletion of the q11.2 region of chromosome 22. Among the many genes in this region, Tbx1 is generally thought to be of particular importance in the etiology of DiGeorge syndrome, in part because mutation of the Tbx1 gene in mouse replicates most of the phenotypes seen in human infants. In mice, mutation of certain other genes also results in DiGeorge syndrome defects, and in every case these have been shown to interact at the molecular level with Tbx1. In this thesis, we describe for the first time that conditional deletion in endothelial cells of a gene unrelated to Tbx1 also causes DiGeorge syndrome malformations in mice. We propose that vascular deficiency can lead to or be a cause of DiGeorge syndrome. ❧ In second part of the thesis, we addressed the requirement for TGFβ signaling in the formation and maintenance of the vascular matrix. We employed lineage-specific mutation of the type II TGFβ receptor gene (Tgfbr2) in vascular smooth muscle precursors in mice. In mesoderm-derived smooth muscle, absence of TGFβ receptor function resulted in a poorly organized vascular elastic matrix in late-stage embryos which was prone to dilation and aneurysm. This defect represents a failure to initiate formation of the elastic matrix, rather than a failure to maintain a preexisting matrix. In mutant tissue, lysyl oxidase expression was substantially reduced, which may contribute to the observed pathology. |
| Keyword | DiGeorge Syndrome; Neuropilin-1; Tbx1 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Zhou, Jingjing |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-ZhouJingji-36.pdf |
Description
| Title | Page 1 |
| Full text | ENDOTHELIAL NEUROPILIN DISRUPTION IN MICE CAUSES DIGEORGE SYNDROME-LIKE MALFORMATIONS INDEPENDENT OF TBX1 by Jingjing Zhou A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partially Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (GENETIC, MOLECULAR, AND CELLULAR BIOLOGY) August 2011 Copyright 2011 Jingjing Zhou |
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