The ability to induce or ablate gene expression in a tissue-specific manner has proven to be a hugely important tool for biologists in many different disciplines. By mating a transgenic mouse in which the Cre recombinase gene is expressed under the control of a tissue-specific promoter to a mouse containing the gene of interest flanked by Cre recognition sites (loxP) an investigator can rapidly and efficiently knock out or induce the gene in a tissue- and/or temporal-specific manner. This conditional transgenesis circumvents some problems associated with whole animal gene knockouts that arise due to embryonic lethality or, involvement of the gene in the biology of multiple tissues. The limiting factor in conditional transgenesis studies is the derivation of mouse strains in which the Cre recombinase is expressed in the appropriate tissue-specific manner. Currently there are no mouse strains available which express the Cre recombinase specifically, or even predominantly, in the gastric epithelium. The lack of this important resource has impaired our ability to clearly understand the physiology and pathophysiology of the gastric mucosa. The goal of this proposal is to develop the technology to target transgene expression to the two predominant cell lineages within the gastric epithelium: the mucous-producing pit cells at the apical surface of the gastric gland and the zymogenic chief cells located towards the base of the gland.
This aim will be achieved by """"""""knocking-in"""""""" a Cre-recombinase cassette into the loci for the trefoil factor 1 and pepsinogen C loci. These mice can then be mated to any mouse strain containing a gene of interest which has been modified to be flanked by loxP recombinase signals. Once derived and characterized, these mice will be highly beneficial to numerous groups working on projects that cross several disciplines including immunology and inflammation, cancer, nutrition, and developmental biology. Thus, development of this unique resource will be of use to investigators supported by multiple NIH Institutes and Centers including NIDDK, NIAID, NCI, and NIGMS. ? ?
