5 minute lightning oral presentation (and poster) ESA-SRB 2023 in conjunction with ENSA

Effects of myocyte-specific deletion of Vitamin D receptors on muscle function and structure in mice (#214)

Miguel Lorenzo Sales Agoncillo 1 , Jennifer Chen 1 , Josephine Yu 1 , Christian Girgis 1 2 3 , Jenny Gunton 1 2 3
  1. The Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. Faculty of Health and Medicine, The University of Sydney, Sydney, NSW, Australia
  3. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia

Vitamin D deficiency is associated with falls, muscle weakness, and sarcopenia. Vitamin D receptor (VDR) deletion in mice reduces their grip strength and endurance.

This project investigates the effects of myocyte-specific Vitamin D receptor deletion (mVDR) on muscle regeneration and function after injury.

Floxed VDR mice and human skeletal actin Cre-recombinase mice were bred to generate mVDR mice. The controls were floxed mice without Cre. Ten-month old males (n = 11-13/group) were injected with Notexin in their right tibialis anterior (TA) to induce myocyte death. Each mouse also had a control injection of saline into the Left TA.

mVDR mice had decreased grip strength (rmANOVA, p<0.01), but there were no significant differences in endurance-distance or voluntary wheel-running. At 28 days, the notexin-treated TA mass in mVDR was 25% lighter than their left-TA control (p=0.045) and 18% heavier than notexin-treated FC mice TA.

Histological analysis of mVDR notexin-treated muscles showed a high proportion of central nuclei, indicating ongoing myocyte regeneration. Two of the mVDR mice had very pronounced fibrosis in their R TA muscle, whereas none of the controls had increased fibrosis.

In summary, mVDR mice showed decreased grip strength but increased TA weight after a notexin-model of muscle injury and regeneration. Further histological assessment will be performed to investigate increased TA mass and muscle morphology.