ORGANIZATION AND ANALYSIS OF THE COMPLETE RAT CALMODULIN-DEPENDENT PROTEIN-KINASE-IV GENE

A 42-kilobase pair region of rat DNA containing the Ca2+/calmodulin-de pendent protein kinase IV (CaM kinase IV) gene has been cloned and cha racterized. The gene consists of 12 exons and 11 introns and is predic ted to encode both beta and cy forms of CaM kinase IV as well as the t estis-specific calmodulin-binding protein calspermin. The promoter uti lized to generate the alpha-kinase isoform is located in intron 1, whe reas the promoter utilized to produce the calspermin transcript is con tained in intron 10. The calspermin promoter region which extends from -200 to +321 relative to the calspermin transcription initiation site that contains two cyclic AMP response elements (CRE) at -70 and -50 a nd has been shown previously to be inactive in NIH3T3 cells (Sun, Z., Sassone-Corsi, P., and Means, A. R. (1995) Mol. Cell. Biol. 15, 561-57 1) was ligated to the lacZ reporter gene and used to generate transgen ic mice. The promoter was expressed exclusively in postmeiotic testis where beta-galactosidase was found predominantly in elongating spermat ids. The cell and developmental specificity of transgene expression wa s very similar to the pattern shown by the endogenous gene. Although t he transgene promoter was silent in somatic tissues, beta-galactosidas e expression could be restored in primary cultures of skin fibroblasts by introduction of vectors encoding CREM tau and CaM kinase IV.