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Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.

Publication ,  Journal Article
Allen, KD; Griffin, TM; Rodriguiz, RM; Wetsel, WC; Kraus, VB; Huebner, JL; Boyd, LM; Setton, LA
Published in: Arthritis Rheum
September 2009

OBJECTIVE: In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be associated with these pathologies. METHODS: Col9a1(-/-) and wild-type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration. RESULTS: Col9a1(-/-) mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1(-/-) mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1(-/-) mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1(-/-) mice having an increased incidence of disc tears. CONCLUSION: These data describe a Col9a1(-/-) behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1(-/-) mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1(-/-) mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.

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Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

September 2009

Volume

60

Issue

9

Start / End Page

2684 / 2693

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Osteoarthritis
  • Motor Activity
  • Models, Genetic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Intervertebral Disc
  • Hyaluronic Acid
 

Citation

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Allen, K. D., Griffin, T. M., Rodriguiz, R. M., Wetsel, W. C., Kraus, V. B., Huebner, J. L., … Setton, L. A. (2009). Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum, 60(9), 2684–2693. https://doi.org/10.1002/art.24783
Allen, Kyle D., Timothy M. Griffin, Ramona M. Rodriguiz, William C. Wetsel, Virginia B. Kraus, Janet L. Huebner, Lawrence M. Boyd, and Lori A. Setton. “Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.Arthritis Rheum 60, no. 9 (September 2009): 2684–93. https://doi.org/10.1002/art.24783.
Allen KD, Griffin TM, Rodriguiz RM, Wetsel WC, Kraus VB, Huebner JL, et al. Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum. 2009 Sep;60(9):2684–93.
Allen, Kyle D., et al. “Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.Arthritis Rheum, vol. 60, no. 9, Sept. 2009, pp. 2684–93. Pubmed, doi:10.1002/art.24783.
Allen KD, Griffin TM, Rodriguiz RM, Wetsel WC, Kraus VB, Huebner JL, Boyd LM, Setton LA. Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum. 2009 Sep;60(9):2684–2693.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

September 2009

Volume

60

Issue

9

Start / End Page

2684 / 2693

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Osteoarthritis
  • Motor Activity
  • Models, Genetic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Intervertebral Disc
  • Hyaluronic Acid