The mouse p97 (CDC48) gene - Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene

Here we present the first description of the genomic organization, transcri ptional regulatory sequences, and adult and embryonic gene expression for t he mouse p97(CDC48) AAA ATPase. Clones representing two distinct p97 genes were isolated in a genomic library screen, one of them likely representing a non-functional processed pseudogene. The coding region of the gene encodi ng the functional mRNA is interrupted by 16 introns and encompasses 20.4 ki lobase pairs. Definition of the transcriptional initiation site and sequenc e analysis showed that the gene contains a TATA-less, CC-rich promoter regi on with an initiator element spanning the transcription start site. Cis-act ing elements necessary for basal transcription activity reside within 410 b ase pairs of the flanking region as determined by transient transfection as says. In immunohistological analyses, p97 was widely expressed in embryos a nd adults, but protein levels were tightly controlled in a cell type- and c ell differentiation-dependent manner. A remarkable heterogeneity in p97 imm unostaining was found on a cellular level within a given tissue, and protei n amounts in the cytoplasm and nucleus varied widely, suggesting a highly r egulated and intermittent function for p97, This study provides the basis f or a detailed analysis of the complex regulation of p97 and the reagents re quired for assessing its functional significance using targeted gene manipu lation in the mouse.