Calcified Tissue International

, Volume 82, Issue 1, pp 66-76

First online:

Phenotypic Characteristics of Bone in Carbonic Anhydrase II-Deficient Mice

  • David S. MargolisAffiliated withOrthopaedic Research Lab, Department of Orthopaedic Surgery, University of Arizona
  • , John A. SzivekAffiliated withOrthopaedic Research Lab, Department of Orthopaedic Surgery, University of Arizona
  • , Li-Wen LaiAffiliated withDepartment of Medicine, University of Arizona
  • , Yeong-Hau H. LienAffiliated withDepartment of Medicine, University of Arizona Email author 

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Carbonic anhydrase II (CAII)-deficient mice were created to study the syndrome of CAII deficiency in humans including osteopetrosis, renal tubular acidosis, and cerebral calcification. Although CAII mice have renal tubular acidosis, studies that analyzed only cortical bones found no changes characteristic of osteopetrosis. Consistent with previous studies, the tibiae of CAII-deficient mice were significantly smaller than those of wild-type (WT) mice (28.7 ± 0.9 vs. 43.6 ± 3.7 mg; p < 0.005), and the normalized cortical bone volume of CAII-deficient mice (79.3 ± 2.2%) was within 5% of that of WT mice (82.7 ± 2.3%; p < 0.05), however, metaphyseal widening of the tibial plateau was noted in CAII-deficient mice, consistent with osteopetrosis. In contrast to cortical bone, trabecular bone volume demonstrated a nearly 50% increase in CAII-deficient mice (22.9 ± 3.5% in CAII, compared to 15.3 ± 1.6% in WT; p < 0.001). In addition, histomorphometry demonstrated that bone formation rate was decreased by 68% in cortical bone (4.77 ± 1.65 μm3/μm2/day in WT vs. 2.07 ± 1.71 μm3/μm2/day in CAII mice; p < 0.05) and 55% in trabecular bone (0.617 ± 0.230 μm3/μm2/day in WT vs. 0.272 ± 0.114 μm3/μm2/day in CAII mice; p < 0.05) in CAII-deficient mice. The number of osteoclasts was significantly increased (67%) in CAII-deficient mice, while osteoblast number was not different from that in WT mice. The metaphyseal widening and changes in the trabecular bone are consistent with osteopetrosis, making the CAII-deficient mouse a valuable model of human disease.


Carbonic anhydrase II Osteopetrosis Renal tubular acidosis Osteoclast Osteoblast