title: Exclusive expression of VMAT2 in noradrenergic neurons increases viability of homozygous VMAT2 knockout mice.
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.
authors: Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Arihisa
authors: A
authors: Ohara
authors: Yoshiyuki
authors: Y
authors: Kasahara
authors: Hideko
authors: H
authors: Yamamoto
authors: Harumi
authors: H
authors: Hata
authors: Hideaki
authors: H
authors: Kobayashi
authors: Yohtaro
authors: Y
authors: Numachi
authors: Ichiro
authors: I
authors: Miyoshi
authors: F Scott
authors: FS
authors: Hall
authors: George R
authors: GR
authors: Uhl
authors: Kazutaka
authors: K
authors: Ikeda
authors: Ichiro
authors: I
authors: Sora
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism*; D000818:Animals; D001259:Ataxia / Q000235:genetics; D005684:Gait / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D019076:Transgenes; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins