and specific aims): The investigators have recently isolated a lung transcription factor, LKLF-1, which belongs to the Kruppel family of transcription factors. Because LKLF-1, is one of the few transcription factors expressed almost exclusively in the lung, studies have been initiated to understand its role in lung specific gene expression and development. In situ analysis of adult lung indicates that it is expressed in epithelial cells including both Clara and type II cells, however, Northern blot analysis also shows that LKLF-1 is expressed in embryos before lung development is apparent and thus this gene may also play an important role in development. Mice lacking LKLF-1 display embryonic lethal phenotype. The LKLF-1 gene thus represents a transcription factor which is undoubtly involved in gene regulation in adult lung but is also critical in other systems during embryonic development.
The specific aims are: 1) to carry out detailed analysis of tissue specific and developmental expression of the LKLF-1 gene using in situ and whole mount hybridization analysis; 2) to further characterize the defect resulting from the lack of LKLF-1 expression in our knockout mice utilizing double knockout ES cells to form chimeric animals, organ cultures and analysis of in vitro hematopoiesis; 3) to characterize the DNA binding and activation domains of LKLF-1; 4) to describe the regulation of the LKLF-1 gene particularly in lung epithelial cells; and 5) to determine the chromosomal location of the mouse and human LKLF-1 genes.
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