description): The goal of this project is to establish the pathophysiologic link between the mutation of the X chromosome and the phenotypic abnormalities in the inherited rickets. The investigators hypothesize that a Pi transport inhibitor, recently isolated from osteoblast conditioned media, in the laboratory is a potential candidate for the mediator of the disease. The goals of this project are to further purify and characterize the renal Pi transport factor, a potential candidate for the mediator of the disease with open column chromatography and successive HPLC steps. Upon achieving sufficient purity, its amino acid sequence will be determined. The sequence will be used to design appropriate primers for use in identification of relevant cDNAs from a murine total embryo cDNA library. Alternatively, PCR of bovine bone, or probing a cDNA library constructed from the investigator's osteoblast cultures will be employed. A major long-term goal is to establish a pathophysiologic link between the PEX mutation, humoral mediation, and the phenotypic abnormalities in the disorder. The findings should provide new insights in the biology of Pi homeostasis, and aid in the functional understanding of XLH.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD035118-02
Application #
2857478
Study Section
Pediatrics Subcommittee (CHHD)
Project Start
1998-01-01
Project End
1999-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Reyes-Mugica, M; Arnsmeier, S L; Backeljauw, P F et al. (2000) Phosphaturic mesenchymal tumor-induced rickets. Pediatr Dev Pathol 3:61-9