Impairment of gastric acid secretion and increase of embryonic lethality in Foxq1-deficient mice.
The mouse Foxq1 gene, also known as Hfh1, encodes a winged helix/forkhead transcription factor. In adult mice, Foxq1 is highly expressed in kidney and stomach. Here, we report that Foxq1 is expressed during prenatal and postnatal stomach development and the transcripts are restricted to acid secreting parietal cells. Mice homozygous for a deletion of the Foxq1 locus on a 129/Sv x C57BL/6J hybrid genetic background display variable phenotypes consistent with requirement of the gene during embryogenesis. Approximately 50% of Foxq1-/- embryos die in utero. Surviving homozygous mutants are normal and fertile, and have a silky shiny coat. Although the parietal cell development is not affected in the absence of Foxq1, there is a lack of gastric acid secretion in response to various secretagogue stimuli. Ultrastructural analysis suggests that the gastric acid secretion defect in Foxq1-deficient mice might be due to impairment in the fusion of cytoplasmic tubulovesicles to the apical membrane of secretory canaliculi.
Institute of Human Genetics, University of Gottingen, Gottingen, Germany. wengel@gwdg.de
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Goering
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Adham
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Pasche
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Manner
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Ochs
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Engel
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Zoll
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003582:Cytogenetics; D017931:DNA Primers / Q000235:genetics; D020964:Embryo Loss / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D051858:Forkhead Transcription Factors; C107579:Foxq1 protein, mouse