We plan to continue an investigation of steroid sulfatase, an enzyme that appears to be of crucial importance in the normal programmed desquamation of stratum corneum. Full length cDNA coding for this enzyme will be cloned and sequenced and then will be used as a probe to study the gene. Specific questions to be addressed will include (a) the nature of the inherited gene defects that abrogate steroid sulfatase activity and thereby cause the skin disease recessive X-linked ichthyosis, (b) the possible location of alleles on the Y as well as X chromosome, and (c) patterns of DNA methylation that may be specific to this gene when on active, as compared to inactive X chromosomes, and when in tissues where the gene product is expressed, as compared to tissues where it is not expressed. The expertise developed during these studies will be applied to an examination of the antigens to which autoimmune antibodies develop in the acquired bullous diseases such as pemphigus. These autoantibodies clearly are the proximate cause of the blistering in at least some of these diseases, but the antigens are poorly characterized. Specifically, the human autoantibodies will be used to select clones containing inserts coding for the relevant antigens from a Lambdagt 11 expression library constructed from cDNA prepared from epidermal mRNA. The full cDNA sequences corresponding to the mRNAs will be sequenced, and patients will be characterized according to the epitopes with which their antibodies react. In the long-term these studies will provide a better understanding of the pathogenesis of these diseases and hopefully thereby will lead to improved methods of treating them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR028069-11
Application #
3155603
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1980-12-01
Project End
1991-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
11
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143