Forty mouse strain survey of voluntary calcium intake, blood calcium, and bone mineral content

Abstract

We measured voluntary calcium intake, blood calcium, and bone mineral content of male and female mice from 40 inbred strains. Calcium intakes were assessed using 48-h two-bottle tests with a choice between water and one of the following: water, 7.5, 25, and 75 mM CaCl(2), then 7.5, 25, and 75 mM calcium lactate (CaLa). Intakes were affected by strain, sex, anion, and concentration. In 11 strains females consumed more calcium than did males and in the remaining 29 strains there were no sex differences. Nine strains drank more CaLa than CaCl(2) whereas only one strain (JF1/Ms) drank more CaCl(2) than CaLa. Some strains had consistently high calcium intakes and preferred all calcium solutions relative to water (e.g., PWK/PhJ, BTBR T(+)tf/J, JF1/Ms). Others had consistently low calcium intakes and avoided all calcium solutions relative to water (e.g., KK/H1J, C57BL/10J, CE/J, C58/J). After behavioral tests, blood was sampled and assayed for pH, ionized calcium concentration, and plasma total calcium concentration. Bone mineral density and content were assessed by DEXA. There were no significant correlations between any of these physiological measures and calcium intake. However, strains of mice that had the highest calcium intakes generally fell at the extremes of the physiological distributions. We conclude that the avidity for calcium is determined by different genetic architecture and thus different physiological mechanisms in different strains.

Fig. 1.

Scatter plot of intake of three concentrations of CaCl₂ versus calcium lactate (CaLa; r=0.75). Each point represents the mean value of ~10 mice of the same sex and strain. The four outlying high points are all from the MSM/MsJ strain. The outlying low point is from C58/J females given 7.5 mM concentrations.

Fig. 2.

Mean CaCl₂ (circles) and CaLa (triangles) intakes (adjusted for bodyweight^0.667) of male (blue) and female (red) mice from 40 strains. Free-standing circles are total water intakes in two-bottle water versus water test. Water intakes for C58/J females (126 mL/kg^0.667) and NZW/LacJ males (139 mL/kg^0.667) are drawn at top of scale because they fall outside range of graph. Vertical lines are standard errors of the mean; these are smaller than the symbols in most cases.

Fig. 3.

Daily intake of three concentrations of calcium by 40 strains of mice (sexes and anion combined). Strains are arranged in order from lowest to highest intake (adjusted for body weight^0.667) of 75 mM Ca²⁺. The scale for the 25 mM calcium concentrations is offset to improve readability. Vertical shaded bars are 95% confidence intervals from the overall mean for each calcium concentration. Horizontal lines are standard errors of the mean; these are smaller than the symbols in most cases.

Fig. 4.

Time required to collect a 40-µl blood sample from the tail for 40 strains of mice. Strains are arranged in order from easiest to most difficult bleeders. Symbols represent average of males and females (~20 mice/strain). Vertical shaded bar shows 95% confidence intervals from the overall mean. Horizontal lines are standard errors of the mean; these are smaller than the symbols in most cases.

Fig. 5.

Blood pH of 40 strains of mice. Strains are arranged in order from lowest to highest pH. Symbols represent average of males and females (~20 mice/strain). Vertical shaded bar shows 95% confidence intervals from the overall mean. Horizontal lines are standard errors of the mean.

Fig. 6.

Blood ionized calcium concentrations of mice from 40 strains. Symbols represent average of males and females (~20 mice/strain). Circles=blood ionized calcium without adjustment for pH. Squares=blood ionized calcium adjusted for pH. Vertical shaded bars show 95% confidence intervals from the overall mean. Horizontal lines are standard errors of the mean.

Fig. 7.

Plasma total calcium concentrations of mice from 40 strains. Strains are arranged in order from lowest to highest plasma total calcium. Symbols represent average of males and females (~20 mice/strain). Vertical shaded bar shows 95% confidence intervals from the overall mean. Horizontal lines are standard errors of the mean.

Fig. 8.

Bone mineral density (BMD; squares) and bone mineral content (BMC; circles) of mice from 40 strains. Strains are arranged in order from lowest to highest BMD. Symbols represent average of males and females (~20 mice/strain). The only strains with sex differences were C57BR/cdJ, C57L/J and KK/H1J for BMD, and C57BRcd/J, NON/LtJ and PERA/EiJ for BMC. Vertical shaded bars show 95% confidence intervals from the overall mean. Horizontal lines are standard errors of the mean; these are smaller than the symbols in most cases.