Exclusive expression of VMAT2 in noradrenergic neurons increases viability of homozygous VMAT2 knockout mice

Arihisa Ohara, Yoshiyuki Kasahara, Hideko Yamamoto, Harumi Hata, Hideaki Kobayashi, Yohtaro Numachi, Ichiro Miyoshi, F. Scott Hall, George R. Uhl, Kazutaka Ikeda, Ichiro Sora

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

The vesicular monoamine transporter 2 (VMAT2) translocates monoamine neurotransmitters from the neuronal cytoplasm into synaptic vesicles. Since VMAT2-/- mice die within a few days of birth, it is difficult to analyze the detailed VMAT2 functions using these mice. In this study, we generated human VMAT2 transgenic mice that expressed VMAT2 in noradrenergic neurons with the aim to rescue the lethality of VMAT2 deletion. The expression of human VMAT2 in noradrenergic neurons extended the life of VMAT2-/- mice for up to three weeks, and these mice showed severe growth deficiency compared with VMAT2+/+ mice. These results may indicate that VMAT2 expressed in noradrenergic neurons has crucial roles in survival during the first several weeks after birth, and VMAT2 functions in other monoaminergic systems could be required for further extended survival. Although VMAT2 rescue in noradrenergic neurons did not eliminate the increased morbidity and lethality associated with VMAT2 deletion, the extension of the lifespan in VMAT2 transgenic mice will enable behavioral, pharmacological and pathophysiological studies of VMAT2 function.

Original languageEnglish
Pages (from-to)526-532
Number of pages7
JournalBiochemical and biophysical research communications
Volume432
Issue number3
DOIs
Publication statusPublished - 2013 Mar 15

Keywords

  • Dopamine
  • Locomotion
  • Monoamine
  • Transgenic

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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