The principal investigator attempts to determine the morphological, biochemical and physiological effects of expression of bone morphogenetic protein-2 (BMP-2) as compared with BMP-4 transgenes produced by coupling the cDNA of these TGF beta gene family members to the cytokeratin IV (CKIV) promoter on vibrissae hair follicles, epidermis and dermis. It will be determined if expression of BMP-2, BMP-4 transgene in the hair follicles of transgenic mice induces abnormal proliferation, keratinization and hair cycle by regulating expression of epidermal growth factor receptors (EGFR) and transforming growth factor alpha (TGF alpha). In addition, the principal investigator intends to determine if ligands of the EGFR, cytokines or pharmacological agents will induce epidermal proliferation, hair follicle growth or normal distribution of cytokeratins in the CKIV BMP-4 transgenic mice. Finally, the investigator will determine if expression of BMP-4 transgene in the hair follicles induces an abnormal inflammatory response around the hair follicles. cDNA from BMP-2 and BMP-4 will be inserted into CLA-I site of the cytokeratin expression vector. The 24 kb fragments containing the promotor region, the BMP-2 or BMP-4 cDNA, and the splice and polynuclear sites will be isolated and used for polynuclear injection to produce transgenic mice. The expression of the transgene will be analyzed by morphologic, histopathologic, morphometric and molecular techniques.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Russell, Shirley B; Smith, Joan C; Huang, Minjun et al. (2015) Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases. PLoS Genet 11:e1005568
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Jandova, Jana; Eshaghian, Alex; Shi, Mingjian et al. (2012) Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry. J Invest Dermatol 132:421-8
Jandova, Jana; Shi, Mingjian; Norman, Kimberly G et al. (2012) Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype. Biochim Biophys Acta 1822:293-300
Sundberg, J P; Taylor, D; Lorch, G et al. (2011) Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans. Vet Pathol 48:513-24
Harries, M J; Sun, J; Paus, R et al. (2010) Management of alopecia areata. BMJ 341:c3671
Yang, Jinming; Splittgerber, Ryan; Yull, Fiona E et al. (2010) Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest 120:2563-74
Russell, Shirley B; Russell, James D; Trupin, Kathryn M et al. (2010) Epigenetically altered wound healing in keloid fibroblasts. J Invest Dermatol 130:2489-96

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