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)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
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
2014-08-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
City
Houston
State
TX
Country
United States
Zip Code
77225
Shalata, Adel; Mahroom, Mohammad; Milewicz, Dianna M et al. (2018) Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype. Orphanet J Rare Dis 13:41
Regalado, Ellen S; Mellor-Crummey, Lauren; De Backer, Julie et al. (2018) Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations. Genet Med 20:1206-1215
Lowey, Susan; Bretton, Vera; Joel, Peteranne B et al. (2018) Hypertrophic cardiomyopathy R403Q mutation in rabbit ?-myosin reduces contractile function at the molecular and myofibrillar levels. Proc Natl Acad Sci U S A 115:11238-11243
Robinet, Peggy; Milewicz, Dianna M; Cassis, Lisa A et al. (2018) Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council. Arterioscler Thromb Vasc Biol 38:292-303
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Tan, Kai Li; Haelterman, Nele A; Kwartler, Callie S et al. (2018) Ari-1 Regulates Myonuclear Organization Together with Parkin and Is Associated with Aortic Aneurysms. Dev Cell 45:226-244.e8
Guo, Dong-Chuan; Regalado, Ellen S; Pinard, Amelie et al. (2018) LTBP3 Pathogenic Variants Predispose Individuals to Thoracic Aortic Aneurysms and Dissections. Am J Hum Genet 102:706-712
Milewicz, Dianna M; Prakash, Siddharth K; Ramirez, Francesco (2017) Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models. Annu Rev Med 68:51-67
Humphrey, Jay D; Milewicz, Dianna M (2017) Aging, Smooth Muscle Vitality, and Aortic Integrity. Circ Res 120:1849-1851
Guo, Dong-Chuan; Duan, Xue-Yan; Regalado, Ellen S et al. (2017) Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease. Am J Hum Genet 100:21-30

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