Foxl1 null mice have abnormal intestinal epithelia, postnatal growth retardation, and defective intestinal glucose uptake.
Mice lacking the mesenchymal winged helix transcription factor Foxl1 exhibit markedly abnormal small intestinal epithelia and postnatal growth retardation. We investigated whether defects in intestinal nutrient uptake and specific transport processes exist in mice homozygous for a Foxl1 null allele (Foxl1-/-). Foxl1-/- mice and controls on a defined genetic background were weighed regularly and killed at 2, 4, and 12 wk of age. Intestinal uptake studies, quantitative real-time PCR, RNase protection assays, and Western blot analyses were performed. Foxl1-/- mice have dysmorphic small intestinal epithelia and postnatal growth retardation. Foxl1-/- mice demonstrate decreased small intestinal uptake of D-glucose in all age groups studied. Intestinal uptake of D-fructose and two amino acids, L-proline and L-leucine, is not altered. Consistent with these findings, Foxl1-/- mice show decreased levels of the intestinal D-glucose transporter SGLT1. Expression of sucrase-isomaltase, lactase, GLUT2, and Na+-K+ ATPase are not changed. Foxl1-/- mice demonstrate markedly abnormal intestinal epithelia, postnatal growth retardation, and decreased intestinal uptake of D-glucose. The specific effect of Foxl1 on intestinal d-glucose uptake is due to decreased production of SGLT1 protein in the small intestine. Thus we identified, for the first time, a link between a mesenchymal factor, Foxl1, and the regulation of a specific epithelial transport process.
Katz
Jonathan P
JP
Dept. of Genetics, Univ. of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104-6145, USA.
Perreault
Nathalie
N
Goldstein
Bree G
BG
Chao
Hann-Hsiang
HH
Ferraris
Ronaldo P
RP
Kaestner
Klaus H
KH
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors; D005947:Glucose / Q000493:pharmacokinetics*; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D043322:Lactase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D013393:Sucrase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D014157:Transcription Factors; D043322:Lactase; D013393:Sucrase; D005947:Glucose