TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury

J Clin Invest. 2002 Jan;109(2):193-204. doi: 10.1172/JCI12529.


Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2, we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities. However, quantitative measurements revealed a significant decrease in gastric mucosal thickness and in gastric mucosal proliferation rates. In addition, there was a twofold increase in activated parietal cells resulting in a twofold increase in basal and stimulated gastric acid output and an undetectable serum gastrin level. The TFF2-deficient mice also showed a significant increase in the degree of gastric ulceration after administration of indomethacin. Taken together, these results suggest a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cell Division
  • Cloning, Molecular
  • Gastric Acid / metabolism*
  • Gastric Mucosa / cytology
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gene Expression
  • Growth Substances / genetics
  • Growth Substances / physiology*
  • Humans
  • Indomethacin / adverse effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucins*
  • Muscle Proteins*
  • Neuropeptides*
  • Parietal Cells, Gastric / metabolism
  • Peptides / genetics
  • Peptides / physiology*
  • RNA, Messenger
  • Sequence Analysis, DNA
  • Stomach / drug effects
  • Stomach / injuries
  • Stomach Ulcer / chemically induced*
  • Trefoil Factor-2
  • Trefoil Factor-3


  • Anti-Inflammatory Agents, Non-Steroidal
  • Growth Substances
  • Mucins
  • Muscle Proteins
  • Neuropeptides
  • Peptides
  • RNA, Messenger
  • TFF2 protein, human
  • TFF3 protein, rat
  • Tff2 protein, rat
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Indomethacin