Surfactant Protein A Promoter Directs The Expression Of The Cre Recombinase In Alveolar Type Ⅱ Cells Of Transgenic Mice

Alveolar type â…¡ cells that synthesize and secrete pulmonary surfactant (SP) play important roles in balancing the function of the lung and are required for the repair after pulmonary damage. Abnormalities in alveolar type â…¡ cells and PS system have been detected in several pulmonary diseases. However, little is known about the roles of alveolar type â…¡ cells in the processes of the lung development, innate immunity and many diseases. The genetic mechanism underlying the function of alveolar type â…¡ cells is also largely unknown.In order to study the genetic mechanism that regulates the function of alveolar type â…¡ cells using the Cre-LoxP system, we generated a transgenic mouse line that expressed the Cre recombinase in the alveolar type â…¡ cells under the control of the mouse surfactant protein A promoter. A Cre transgenic construct containing the SP-A promoter, Cre recombinase gene and the polyA of human growth hormone gene was generated. The linearized constructs were introduced into 808 fertilized zygotes by microinjection. 729 of these injected eggs were implanted into the oviducts of 36 female mice and 133 offspring were obtained. 11 founder mice carrying the Cre gene were identified by PCR and Southern blot. The SP-A-Cre transgenic founder mice were crossed with the mouse strain carrying the Smad4 conditional alleles and the reporter mouse line ROSA26 to check the tissue distribution and excision activity of the Cre recombinase. The results showed that 2 independent transgenic lines with different expression pattern of Cre recombinase were obtained. The SP-A-Crel transgenic mice expressed the Cre recombinase in lung, brain and gastrointestinal tract where the SP-A normally expressed, while restricted Cre activity can only be detected in lung in SP-A-Cre2 transgenic mice. The SP-A-Crel mice were crossed with Smad4^co,co mice to generate SP-A-...