VAMP3 Null Mice Display Normal Constitutive, Insulin- and Exercise-Regulated Vesicle Trafficking

Abstract

To investigate the physiological function of the VAMP3 vesicle SNARE (v-SNARE) isoform in the regulation of GLUT4 vesicle trafficking, we generated homozygotic VAMP3 null mice by targeted gene disruption. The VAMP3 null mice had typical growth rate and weight gain, with normal maintenance of fasting serum glucose and insulin levels. Analysis of glucose disposal and insulin sensitivity demonstrated normal insulin and glucose tolerance, with no evidence for insulin resistance. Insulin stimulation of glucose uptake in isolated primary adipocytes was essentially the same for the wild-type and VAMP3 null mice. Similarly, insulin-, hypoxia-, and exercise-stimulated glucose uptake in isolated skeletal muscle did not differ significantly. In addition, other general membrane trafficking events including phagocytosis, pinocytosis, and transferrin receptor recycling were also found to be unaffected in the VAMP3 null mice. Taken together, these data demonstrate that VAMP3 function is not necessary for either regulated GLUT4 translocation or general constitutive membrane recycling.

ACKNOWLEDGMENTS

We thank Diana Boeglin for assistance with the glucose tolerance and insulin tolerance tests. We also thank Ann Davis (Bayer) for helpful discussion the design of the VAMP3 targeting vector.

This work was supported by research grants DK33823, DK55811, and DK25295 from the National Institutes of Health. S.M. is a recipient of a postdoctoral fellowship (Formación de Personal Investigador) from the Ministerio de Educación y Cultura, Spain. L.-A.A. is a recipient of a Merit Review award from the Veterans Administration.