In the long term I want to understand the molecular basis of the heritable forms of combined pituitary hormone deficiency, a disorder usually due to the lack of several anterior pituitary cell types. Recently a candidate gene, Prophet of Pit-1 (prop-1) encoding a homeodomain transcription factor, was cloned by the sponsor's laboratory. A point mutation in the homeodomain of Prop-1 found in Ames mice can still bind to Prop-1 consensus sites. To fully understand the role of Prop-1 in pituitary cell lineage determination, the following specific objectives are proposed:
Aim1 : To generate mice deficient in Prop-1, to determine pituitary hormone deficiency phenotypes. I will also knock-in a B-lacatamase (beta- lac) reporter gene into the locus simultaneously, so that I can purify the Prop-1 expressing cells using fluorescence activated cell sorting (FACS) technique;
Aim2 : To identify Prop-1 target genes using representational difference analysis (RDA), a PCR-based subtractive hybridization strategy allowing identification of transcripts that exhibit 10-fold or greater differences in their concentrations between two different sources;
Aim3 : to rescue depleted Pit-1 dependent cell lineages in the Prop-1 mutant by knock-in of Pit-1 into the Prop-1 locus through homologous recombination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK009814-01
Application #
2708025
Study Section
Special Emphasis Panel (ZRG2-REB (01))
Program Officer
Hyde, James F
Project Start
1999-03-05
Project End
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Li, Xue; Perissi, Valentina; Liu, Forrest et al. (2002) Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science 297:1180-3