Disruption of the Golgi protein Otg1 gene causes defective hormone secretion and aberrant glucose homeostasis in mice.
BACKGROUND
Concerted hormone secretion is essential for glucose homeostasis and growth. The oocyte testis gene 1 (Otg1) has limited information in mammals before. Human OTG1 has been identified as an antigen associated with cutaneous T cell lymphoma, while worm Otg1 is recently reported to be a vesicle trafficking regulator in neurons. To understand the physiological role of Otg1 and its potential relation to hormone secretion, we characterized a mutation caused by the piggyBac transposon (PB) insertion in mice.


RESULTS
Oocyte testis gene 1 encodes a Golgi localized protein that is expressed with a broad tissue distribution in mice. The PB insertion effectively blocks Otg1 expression, which results in postnatal lethality, growth retardation, hypoglycemia and improved insulin sensitivity in mice. Otg1 mutants exhibit decreased levels of insulin, leptin and growth hormone in the circulation and reduced hepatic IGF-1 expression. Decreased expression of Otg1 in pituitary GH3 cells causes reduced grow hormone expression and secretion, as well as the traffic of the VSVG protein marker.


CONCLUSIONS
Our data support the hypothesis that Otg1 impacts hormone secretion by regulating vesicle trafficking. These results revealed a previously unknown and important role of Otg1 in hormone secretion and glucose homeostasis in mammals.
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.
Guangxue
G
Wang
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.
Rongbo
R
Li
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.
Ying
Y
Yang
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.
Liang
L
Cai
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06536 USA.
Sheng
S
Ding
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.|Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06536 USA.
Tian
T
Xu
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.|Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309 USA.
Min
M
Han
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433 China.
Xiaohui
0000-0002-1801-9645
X
Wu
Hypoglycemia; Hypoinsulinemia; Otg1; Vesicle trafficking