Abstract

The goal of this project is to elucidate protein and gene structures for novel components of the cutaneous basement membrane zone. Novel proteins of the skin basement membrane zone are constantly being discovered. The information on these new proteins and genes is fundamental to the study of mutations in EB. During the past four years, we have characterized a number of normal basement membrane genes. The gene probes developed in this project are instrumental in the molecular characterization of EB mutations. In this renewal application, we propose to use the same strategies to characterize additional basement membrane zone genes. Our initial efforts will be directed toward completing the current studies on the genes for the 230-kDa and 180-kDa bullous pemphigoid antigens (BPAG1 and BPAG2, respectively). At the same time, we will continue the work we have initiated towards characterizing a new basemetn membrane protein, BM90, and a related gene that we have discovered during the course of this study. We will then proceed to isolate cDNA and genomic clones for one or more novel components in skin such as type XIV collagen, kalinin/epiligrin, or other new proteins in the skin basement membrane zone.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR038923-14
Application #
6299817
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
14
Fiscal Year
2000
Total Cost
$144,808
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Type
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

Mahoney, My G; Sadowski, Sara; Brennan, Donna et al. (2010) Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest Dermatol 130:968-78
Chung, Hye Jin; Uitto, Jouni (2010) Epidermolysis bullosa with pyloric atresia. Dermatol Clin 28:43-54
Chung, Hye Jin; Uitto, Jouni (2010) Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin 28:93-105
Remington, Jennifer; Wang, Xinyi; Hou, Yingpin et al. (2009) Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa. Mol Ther 17:26-33
Uitto, Jouni (2009) Progress in heritable skin diseases: translational implications of mutation analysis and prospects of molecular therapies*. Acta Derm Venereol 89:228-35
Lugassy, Jennie; McGrath, John A; Itin, Peter et al. (2008) KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome. J Invest Dermatol 128:1517-24
Igoucheva, Olga; Kelly, Aislinn; Uitto, Jouni et al. (2008) Protein therapeutics for junctional epidermolysis bullosa: incorporation of recombinant beta3 chain into laminin 332 in beta3-/- keratinocytes in vitro. J Invest Dermatol 128:1476-86
Nakajima, Koji; Tamai, Katsuto; Yamazaki, Takehiko et al. (2008) Identification of Skn-1n, a splice variant induced by high calcium concentration and specifically expressed in normal human keratinocytes. J Invest Dermatol 128:1336-9
Varki, Roslyn; Sadowski, Sara; Uitto, Jouni et al. (2007) Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes. J Med Genet 44:181-92
Nyquist, Gurston G; Mumm, Christina; Grau, Renee et al. (2007) Malignant proliferating pilar tumors arising in KID syndrome: a report of two patients. Am J Med Genet A 143:734-41

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