International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

I33. The Role of Mouse Forkhead Homolog-6(Fkh6) Gene Product in Growth Control of Gastrointestinal Tract

Haruhiko Koseki, Katsuyuki Fukuda, Taka-aki Furumoto
Graduate School of Medicine, Chiba Univ.

Several studies using knock out mice have revealed that winged helix forkhead proteins play important roles in organogenesis and maintenance of cell functions through the transcriptional regulation .Forkhead homolog-6(Fkh6) is expressed in gastrointestinal tract, lung and kidney. In gastrointestinal tract, Fkh6 gene is exclusively expressed in the mesenchyme. We generated mice lacking a functional product of Fkh6 gene by homologous recombination to investigate the role of Fkh6 gene product in gastrointestinal development. Fkh6 mutant mice exhibit retardation in post natal growth. In investigation of gastrointestinal tract of Fkh6 mutant mice , grandular stomach epitherial cells exhibit increased proliferation with disordered grandular structure and thickened mucosae. Functional analysis demonstrated that both basal and stimulated hydrochloric acid secretion was almost completely supressed in Fkh6 mutant. Furthermore Peyer's patches are decreased in number and formed poorly in mutant. Many polyp like elevations are observed in colonic lumen, it shows lymph follicle structurelly.

These results show that mesenchymal Fkh6 gene plays important roles in morphogenesis of grandular stomach epithelium and gut associated lymphoid tissue. Fkh6 mutant mice are thought to be very useful model in investigating signaling cascade that mediates communications between the tissues to regulate morphogenesis and immunity of gut.


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