Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition

A. M. Taylor, A. J. Preston, N. K. Paulk, H. Sutherland, C. M. Keenan, P. J M Wilson, B. Wlodarski, Markus Grompe, L. R. Ranganath, J. A. Gallagher, J. C. Jarvis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design: The homogentisate 1,2-dioxygenase Hgd +/-Fah -/- mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl's reagent. Results: Early time point observations at 8. months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13. months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions: Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy.

Original languageEnglish (US)
Pages (from-to)880-886
Number of pages7
JournalOsteoarthritis and Cartilage
Volume20
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Ochronosis
Alkaptonuria
Tissue
Tyrosinemias
Kidney
Homogentisate 1,2-Dioxygenase
Inborn Genetic Diseases
Fibula
Joint Diseases
Hematoxylin
Eosine Yellowish-(YS)
Chondrocytes
Rare Diseases
Femur
Microscopic examination
Genotype

Keywords

  • Alkaptonuria
  • Arthritis
  • Arthropathy
  • Mouse model
  • Ochronosis

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Taylor, A. M., Preston, A. J., Paulk, N. K., Sutherland, H., Keenan, C. M., Wilson, P. J. M., ... Jarvis, J. C. (2012). Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition. Osteoarthritis and Cartilage, 20(8), 880-886. https://doi.org/10.1016/j.joca.2012.04.013

Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition. / Taylor, A. M.; Preston, A. J.; Paulk, N. K.; Sutherland, H.; Keenan, C. M.; Wilson, P. J M; Wlodarski, B.; Grompe, Markus; Ranganath, L. R.; Gallagher, J. A.; Jarvis, J. C.

In: Osteoarthritis and Cartilage, Vol. 20, No. 8, 08.2012, p. 880-886.

Research output: Contribution to journalArticle

Taylor, AM, Preston, AJ, Paulk, NK, Sutherland, H, Keenan, CM, Wilson, PJM, Wlodarski, B, Grompe, M, Ranganath, LR, Gallagher, JA & Jarvis, JC 2012, 'Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition', Osteoarthritis and Cartilage, vol. 20, no. 8, pp. 880-886. https://doi.org/10.1016/j.joca.2012.04.013
Taylor, A. M. ; Preston, A. J. ; Paulk, N. K. ; Sutherland, H. ; Keenan, C. M. ; Wilson, P. J M ; Wlodarski, B. ; Grompe, Markus ; Ranganath, L. R. ; Gallagher, J. A. ; Jarvis, J. C. / Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition. In: Osteoarthritis and Cartilage. 2012 ; Vol. 20, No. 8. pp. 880-886.
@article{76670022b27a45a1b358efa75914ef6b,
title = "Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition",
abstract = "Objective: Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design: The homogentisate 1,2-dioxygenase Hgd +/-Fah -/- mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl's reagent. Results: Early time point observations at 8. months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13. months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions: Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy.",
keywords = "Alkaptonuria, Arthritis, Arthropathy, Mouse model, Ochronosis",
author = "Taylor, {A. M.} and Preston, {A. J.} and Paulk, {N. K.} and H. Sutherland and Keenan, {C. M.} and Wilson, {P. J M} and B. Wlodarski and Markus Grompe and Ranganath, {L. R.} and Gallagher, {J. A.} and Jarvis, {J. C.}",
year = "2012",
month = "8",
doi = "10.1016/j.joca.2012.04.013",
language = "English (US)",
volume = "20",
pages = "880--886",
journal = "Osteoarthritis and Cartilage",
issn = "1063-4584",
publisher = "W.B. Saunders Ltd",
number = "8",

}

TY - JOUR

T1 - Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition

AU - Taylor, A. M.

AU - Preston, A. J.

AU - Paulk, N. K.

AU - Sutherland, H.

AU - Keenan, C. M.

AU - Wilson, P. J M

AU - Wlodarski, B.

AU - Grompe, Markus

AU - Ranganath, L. R.

AU - Gallagher, J. A.

AU - Jarvis, J. C.

PY - 2012/8

Y1 - 2012/8

N2 - Objective: Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design: The homogentisate 1,2-dioxygenase Hgd +/-Fah -/- mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl's reagent. Results: Early time point observations at 8. months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13. months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions: Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy.

AB - Objective: Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design: The homogentisate 1,2-dioxygenase Hgd +/-Fah -/- mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl's reagent. Results: Early time point observations at 8. months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13. months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions: Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy.

KW - Alkaptonuria

KW - Arthritis

KW - Arthropathy

KW - Mouse model

KW - Ochronosis

UR - http://www.scopus.com/inward/record.url?scp=84863003048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863003048&partnerID=8YFLogxK

U2 - 10.1016/j.joca.2012.04.013

DO - 10.1016/j.joca.2012.04.013

M3 - Article

C2 - 22542924

AN - SCOPUS:84863003048

VL - 20

SP - 880

EP - 886

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

SN - 1063-4584

IS - 8

ER -