Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density.
To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.
Phillips
C L
CL
Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65212, USA. phillipsca@missouri.edu
Bradley
D A
DA
Schlotzhauer
C L
CL
Bergfeld
M
M
Libreros-Minotta
C
C
Gawenis
L R
LR
Morris
J S
JS
Clarke
L L
LL
Hillman
L S
LS
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000097:blood / Q000652:urine; D002712:Chlorides / Q000032:analysis; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D005269:Femur / Q000737:chemistry / Q000473:pathology*; D005459:Fluorides / Q000032:analysis; D005838:Genotype; D006706:Homeostasis / Q000502:physiology; D007180:Incisor / Q000737:chemistry / Q000473:pathology*; D007408:Intestinal Absorption; D008274:Magnesium / Q000032:analysis / Q000097:blood / Q000652:urine; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008903:Minerals / Q000493:pharmacokinetics; D009501:Neutron Activation Analysis; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D010758:Phosphorus / Q000032:analysis / Q000097:blood / Q000652:urine; D011188:Potassium / Q000032:analysis; D012964:Sodium / Q000032:analysis
D002712:Chlorides; D008903:Minerals; D010758:Phosphorus; D003094:Collagen; D012964:Sodium; D008274:Magnesium; D005459:Fluorides; D011188:Potassium; D002118:Calcium