Bone histomorphometric and biomechanical abnormalities in mice homozygous for deletion of the dopamine transporter gene

Dopamine (DA) has been reported to have effects on calcium and phosphorus m etabolism. The dopamine transporter (DAT) is believed to control the tempor al and spatial activity of released DA by rapid uptake of the neurotransmit ter into presynaptic terminals. We have evaluated the histologic and biomec hanical properties of the skeleton in mice homozygous for deletion of the D A transporter gene (DAT) to help delineate the role of DA in bone biology. We have demonstrated that DAT(-/-) mice have reduced bone mass and strength . DAT(-/-) animals had shorter femur length and dry weight. Ash calcium con tent of the femur was 32% lower in the DAT(-/-) mice than in the wild-type animals. Cancellous bone volume in the proximal tibial metaphysis was signi ficantly lower in the DAT(-/-) animals (p, < 0.04). There was a 32% reducti on in trabecular thickness (p = NS), For the vertebrae, cancellous bone vol ume was again lower in the DAT(-/-) animals compared with wild-type as a co nsequence of increased trabecular spacing (p < 0.05) and reduced trabecular number (p < 0.05). Cortical thickness and bone area in the femoral diaphys is were reduced in the DAT(-/-) animals. The ultimate bending load (femoral strength) for the DAT(-/-) mice was 30% lower than the wild-type mice (p = 0.004). Thus, deletion of the DAT gene results in deficiencies in skeletal structure and integrity. (C) 2000 by Elsevier Science Inc. All rights rese rved.