CLONING AND TISSUE-SPECIFIC EXPRESSION OF THE CDNA FOR THE MOUSE CLARA CELL 10 KD PROTEIN - COMPARISON OF ENDOGENOUS EXPRESSION TO RABBIT UTEROGLOBIN PROMOTER-DRIVEN TRANSGENE EXPRESSION

Uteroglobin (UG) is a hormonally regulated secretory protein produced in the lung and urogenital system of rabbits. It is homologous to rat and human Clara cell 10 kD protein (CC10); however, there are signific ant differences in the tissue-specific expression between these specie s. Mouse CC10 (mCC10) protein has been less well characterized. In thi s study, we cloned and sequenced the cDNA encoding the mCC10 protein. The mouse cDNA showed 90, 52, and 51% amino acid homology to rat and h uman CC10 and rabbit UG cDNA, respectively. The cellular and tissue-sp ecific expression of mCC10 was examined in adult and developing mice. Endogenous mCC10 expression was compared with transgenic mice expressi ng a fusion gene of the rabbit 3.3 kb UG promoter linked to human grow th hormone (hGH) as an easily detectable marker. Northern blot analysi s detected mCC10 mRNA only in the lung. hGH mRNA was detected in the l ung in levels similar to the endogenous mCC10 transcripts. However, it was also present in trace quantities in the uterus and ovary of norma l adult female mice and in the epididymus of adult male mice. hGH and mCC10 proteins were identified in the trachea and lung, where they wer e localized to Clara cells. Ultrastructurally, hGH was present in secr etory granules in the Clara cell cytoplasm and appeared to be secreted into the airways. hGH was initially detectable in 16 day gestation de veloping mice; however, CC10 was not detectable until the eighteenth d ay of gestation. We have created an attractive model for comparing the cis-acting DNA elements governing the interspecies variation in tissu e-specific expression of CC10.