title: Increased connective tissue extracellular matrix in the op/op model of osteopetrosis.
abstract: Mice that are homozygous for the recessive osteopetrosis spontaneous mutation (op/op) develop severe osteopetrosis due to a defect in the production of macrophage colony-stimulating factor (M-CSF) and a deficiency in monocyte-derived osteoclasts. Our study describes a novel soft tissue finding in an osteopetrosis (B6C3Fe a/a-Csf1(op)/J) mouse model. Tissues were obtained from B6C3Fe a/a-Csf1(op)/J mice and age-matched wild-type mice, processed for hematoxylin and eosin sections, and comprehensive light microscopic tissue evaluation was performed. Mutant mice had characteristic traits of op/op deficiency including missing incisors and domed skulls. Histologically, the bone marrow cavity was effaced by interweaving thick bony trabeculae consistent with osteopetrosis. An increase in a finely granular, basophilic interstitial extracellular matrix (ECM) was observed in the subcutaneous connective tissue of the op/op mice when compared with controls. Histochemically, the ECM was negative with periodic acid Schiff and stained dark blue with alcian blue at a pH of 2.5, indicating that it is composed primarily of nonsulfated glycosaminoglycans (GAGs). This work suggests an increased ECM that is composed mainly of GAGs located in the subcutaneous tissue in op/op mice. This increase in ECM may be related to altered matrix production or turnover because of changes in M-CSF production.
authors: Pfizer Global Research and Development, Drug Safety Research and Development, St. Louis, MO 63017, USA. zaher.radi@pfizer.com
authors: Zaher A
authors: ZA
authors: Radi
authors: Roberto E
authors: RE
authors: Guzman
authors: Rosonald R
authors: RR
authors: Bell
mesh_terms: D000818:Animals; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D006025:Glycosaminoglycans; D016173:Macrophage Colony-Stimulating Factor