The UTHSC-Mouse Model Core Laboratory (Core C) will be directed by Dr. Eva M. Zsigmond. Dr. Zsigmond has extensive experience in the generation, identification and breeding of both transgenic and gene-targeted mouse models.
The specific aims of the Core C are the following: 1. Generate knock-in mice carrying Acta2 or Myhll mutations. 2. Breed and maintain appropriate lines of these genetically-manipulated mice for various projects within the program. Core C will provide overall colony maintenance and the testing needed for the backcrossing of the colony. 3. Collect, store and make mouse tissues and primary cells available to the other projects. Core C will explant smooth muscle cells from the mouse aortas and provide these primary cultures from the genetically altered mouse models to the PPG investigators.

Public Health Relevance

Centralizing the generation of animal models for this PPG in one core facility will result in significant savings of time and money. The availability of mouse models of the ACTA2 or MYH11 gene dysfunctions will provide the PPG investigators with unique animal models for their studies of the physiological and pathophysiological roles of the vascular smooth muscle cells in aortic aneurysms, strokes and other cardiovascular artery diseases.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01HL110869-03
Application #
8726469
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
City
Houston
State
TX
Country
United States
Zip Code
77225
Milewicz, Dianna M; Regalado, Ellen S; Shendure, Jay et al. (2014) Successes and challenges of using whole exome sequencing to identify novel genes underlying an inherited predisposition for thoracic aortic aneurysms and acute aortic dissections. Trends Cardiovasc Med 24:53-60
Kwartler, Callie S; Chen, Jiyuan; Thakur, Dhananjay et al. (2014) Overexpression of smooth muscle myosin heavy chain leads to activation of the unfolded protein response and autophagic turnover of thick filament-associated proteins in vascular smooth muscle cells. J Biol Chem 289:14075-88
Qiao, Yan-Ning; He, Wei-Qi; Chen, Cai-Ping et al. (2014) Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure. J Biol Chem 289:22512-23
Regalado, Ellen S; Guo, Dong-chuan; Estrera, Anthony L et al. (2014) Acute aortic dissections with pregnancy in women with ACTA2 mutations. Am J Med Genet A 164A:106-12
Tsai, Ming-Ho; Chang, Audrey N; Huang, Jian et al. (2014) Constitutive phosphorylation of myosin phosphatase targeting subunit-1 in smooth muscle. J Physiol 592:3031-51
Nelson, Michael D; Rader, Florian; Tang, Xiu et al. (2014) PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085-91
Guo, Dong-chuan; Regalado, Ellen; Casteel, Darren E et al. (2013) Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet 93:398-404
Gao, Ning; Huang, Jian; He, Weiqi et al. (2013) Signaling through myosin light chain kinase in smooth muscles. J Biol Chem 288:7596-605
Kuang, Shao-Qing; Geng, Liang; Prakash, Siddharth K et al. (2013) Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade. Arterioscler Thromb Vasc Biol 33:2172-9
Barua, Bipasha; Fagnant, Patricia M; Winkelmann, Donald A et al. (2013) A periodic pattern of evolutionarily conserved basic and acidic residues constitutes the binding interface of actin-tropomyosin. J Biol Chem 288:9602-9

Showing the most recent 10 out of 12 publications