Spatiotemporal Analysis of Cdk5/p35 Knock-in-Cre Mice Reveals Its Novel Expression Pattern

Cyclin-dependent kinase 5 (Cdk5) is chiefly considered a neuronal kinase that is not involved in the cell cycle, like other Cdks, but is instead most active in post-mitotic neurons. Cdk5 is expressed in all the cells, while its main protein activator p35, a non-cyclin regulatory subunit, is expressed predominantly in neurons. Nonetheless, p35 expression has been detected in pancreatic β-cells, podocytes, and lymphocytes, which suggests non-neuronal roles for Cdk5/p35 activity. Due to its potentially important role in tissue development and homeostasis, we wanted to track Cdk5 activity in mice by following the expression of its key activator p35. Thereby, we knocked in the Cre recombinase under the p35 promoter and bred the resulting p35-KI-Cre mice to the lacZ reporter strain. β-gal staining was seen not only in neuronal tissues, but also in several non-neuronal tissues. The staining in non-neuronal tissues further illustrates that Cdk5/p35 activity has broader functions beyond regulating neural processes. Notably, we identified novel p35-lineage cells within the salivary gland embryonic epithelial end buds and in the adult acinar cells. The p35-KI-Cre mice thereby provide a valuable tool to determine in which cell types Cdk5/p35 kinase is active.