Neuroanatomical characterization of a growth hormone secretagogue receptor‐green fluorescent protein reporter mouse

Journal of Comparative Neurology - Tập 522 Số 16 - Trang 3644-3666 - 2014
Bharath K. Mani1, Angela K. Walker1, Eduardo Javier López Soto2, Jesica Raingo2, Charlotte E. Lee1, Mario Perelló3, Zane B. Andrews4, Jeffrey M. Zigman1
1Division of Hypothalamic Research and Division of Endocrinology and Metabolism, Department of Internal Medicine and Department of Psychiatry University of Texas Southwestern Medical Center Dallas Texas 75390‐9077
2Laboratory of Electrophysiology Multidisciplinary Institute of Cell Biology CP 1900 Buenos Aires Argentina
3Laboratory of Neurophysiology Multidisciplinary Institute of Cell Biology CP 1900 Buenos Aires Argentina
4Department of Physiology, Faculty of Medicine Monash University Melbourne 3800 Victoria Australia

Tóm tắt

ABSTRACTGrowth hormone secretagogue receptor (GHSR) 1a is the only molecularly identified receptor for ghrelin, mediating ghrelin‐related effects on eating, body weight, and blood glucose control, among others. The expression pattern of GHSR within the brain has been assessed previously by several neuroanatomical techniques. However, inherent limitations to these techniques and the lack of reliable anti‐GHSR antibodies and reporter rodent models that identify GHSR‐containing neurons have prevented a more comprehensive functional characterization of ghrelin‐responsive neurons. Here we have systematically characterized the brain expression of an enhanced green fluorescence protein (eGFP) transgene controlled by the Ghsr promoter in a recently reported GHSR reporter mouse. Expression of eGFP in coronal brain sections was compared with GHSR mRNA expression detected in the same sections by in situ hybridization histochemistry. eGFP immunoreactivity was detected in several areas, including the prefrontal cortex, insular cortex, olfactory bulb, amygdala, and hippocampus, which showed no or low GHSR mRNA expression. In contrast, eGFP expression was low in several midbrain regions and in several hypothalamic nuclei, particularly the arcuate nucleus, where robust GHSR mRNA expression has been well‐characterized. eGFP expression in several brainstem nuclei showed high to moderate degrees of colocalization with GHSR mRNA labeling. Further quantitative PCR and electrophysiological analyses of eGFP‐labeled hippocampal cells confirmed faithful expression of eGFP within GHSR‐containing, ghrelin‐responsive neurons. In summary, the GHSR‐eGFP reporter mouse model may be a useful tool for studying GHSR function, particularly within the brainstem and hippocampus; however, it underrepresents GHSR expression in nuclei within the hypothalamus and midbrain. J. Comp. Neurol. 522:3644–3666, 2014. © 2014 Wiley Periodicals, Inc.

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Journal of Comparative Neurology

Tập 522 Số 16

3644-3666

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