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Murine TNF(DeltaARE) Crohn's disease model displays diminished expression of intestinal Ca2+ transporters

Sylvie Huybers1, Maria Apostolaki, Bram C J van der Eerden

  • 1Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.

Inflammatory Bowel Diseases
|February 13, 2008
PubMed
Abstract

Insights

Mice with a tumor necrosis factor (TNF) deletion show impaired calcium (Ca2+) handling, reduced vitamin D, and bone abnormalities, mimicking Crohn's disease complications.

Area of Science:

  • Biochemistry
  • Physiology
  • Genetics

Background:

  • Crohn's disease (CD) is linked to low bone density, but its cause is unclear.
  • Mice with a tumor necrosis factor (TNF) deletion (TNF(DeltaARE/+)) model human CD with high TNF-alpha and ileitis.
  • This study investigates Ca(2+) homeostasis in TNF(DeltaARE/+) mice to understand CD-related bone complications.

Purpose of the Study:

  • To analyze Ca(2+) homeostasis in heterozygous TNF(DeltaARE/+) mice.
  • To compare Ca(2+) handling and bone parameters in TNF(DeltaARE/+) mice versus wildtype littermates.
  • To determine if TNF(DeltaARE/+) mice exhibit Ca(2+) absorption or bone resorption issues.

Main Methods:

  • Measured serum Ca(2+) and vitamin D levels.
  • Quantified Ca(2+) transporter gene and protein expression in the intestine, kidney, and bone.
  • Utilized quantitative real-time PCR, Western blot, immunohistochemistry, and microcomputed tomography bone scans.

Main Results:

  • TNF(DeltaARE/+) mice showed reduced duodenal and renal Ca(2+) transporter mRNA and protein expression (e.g., TRPV6, calbindin-D(9K), PMCA1b, calbindin-D(28K), NCX1).
  • Serum 1,25(OH)(2)D(3) levels were significantly reduced in TNF(DeltaARE/+) mice.
  • Bone scans revealed decreased bone thickness and volume, with increased deoxypyridinoline, indicating enhanced bone resorption.

Conclusions:

  • TNF(DeltaARE/+) mice exhibit disturbed Ca(2+) homeostasis, characterized by impaired intestinal and renal Ca(2+) transport.
  • Reduced vitamin D levels contribute to the observed Ca(2+) handling deficits.
  • These mice display significant bone abnormalities, including reduced bone mass and increased resorption, mirroring complications seen in Crohn's disease patients.

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