Partial weight suspension: a novel murine model for investigating adaptation to reduced musculoskeletal loading

Abstract

We developed a new model of hypodynamic loading to support mice in chronic conditions of partial weight bearing, enabling simulations of reduced gravity environments and related clinical conditions. The novel hardware allows for reduced loading between 10 and 80% of normal body weight on all four limbs and enables characteristic quadrupedal locomotion. Ten-week-old female BALB/cByJ mice were supported for 21 days under Mars-analog suspension (38% weight bearing) and compared with age-matched and jacketed (100% weight bearing) controls. After an initial adaptation, weight gain did not differ between groups, suggesting low levels of animal stress. Relative to age-matched controls, mice exposed to Mars-analog loading had significantly lower muscle mass (-23% gastrocnemius wet mass, P < 0.0001); trabecular and cortical bone morphology (i.e., trabecular bone volume: -24% at the distal femur, and cortical thickness: -11% at the femoral midshaft, both P < 0.001); and biomechanical properties of the femoral midshaft (i.e., -27% ultimate moment, P < 0.001). Bone formation indexes were decreased compared with age-matched full-weight-bearing mice, whereas resorption parameters were largely unchanged. Singly housed, full-weight-bearing controls with forelimb jackets were largely similar to age-matched, group-housed controls, although a few variables differed and warrant further investigation. Altogether, these data provide strong rationale for use of our new model of partial weight bearing to further explore the musculoskeletal response to reduced loading environments.

Fig. 1.

A: Partial Weight Suspension habitat with polycarbonate walls, perforated PVC floor and lid, and aluminum channel supporting suspension hardware. Note that holes in this drawing are oversized. Actual openings are 4.8 mm in diameter and allow for passive passage of waste without risk of injury to the animals. B: system for measuring effective body mass. Animals were suspended above a scale, and spring tension was adjusted to provide the desired level of partial weight bearing. [Image credit: Shaun Modi]

Fig. 2.

Relationship between peak vertical ground reaction forces and simulated gravity level, where 1 g represents full weight bearing. Data come from repeated trials in the same animal. Dotted trend line represents a hypothesized linear relationship between the two variables. BW, body weight. Error bars represent ± SD.

Fig. 3.

Daily body mass for 21-day Mars-analog suspension study in female mice. After an initial adaptation period, Mars animals (■) showed similar maintenance of weight as Age-matched controls (△). Jacket animals (♦) gained significantly more weight in the same period. Error bars represent ± SE. *Body mass significantly different from that of Age controls (P < 0.05).