Distribution of estrogen receptor β containing cells in the brains of bacterial artificial chromosome transgenic mice.
In the brain, estrogen receptor beta (ERbeta) plays important roles in autonomic functions, stress reactivity and learning and memory processes. However, understanding the function of ERbeta has been restricted by the limited availability of specific antisera, by difficulties discriminating the discrete localization of ERbeta-immunoreactivity (ir) at the light microscopic level in many brain regions and the identification of ERbeta-containing neurons in neurophysiological and molecular studies. Here, we demonstrate that a Esr2 bacterial artificial chromosome (BAC) transgenic mouse line that expresses ERbeta identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, ERbeta-EGFP was detected in the nuclei and cytoplasm of cells, the majority of which resembled neurons. EGFP often extended into dendritic processes and could be identified either natively or following intensification of EGFP using immunolabeling. The distribution of ERbeta-EGFP cells in brain closely corresponded to that reported for ERbeta protein and mRNA. In particular, ERbeta-EGFP cells were found in autonomic brain regions (i.e., hypothalamic paraventricular nucleus, rostral ventrolateral medulla and nucleus of the solitary tract), in regions associated with anxiety and stress behaviors (i.e., bed nucleus of the stria terminalis, amygdala, periaqueductal gray, raphe and parabrachial nuclei) and in regions involved in learning and memory processes (i.e., basal forebrain, cerebral cortex and hippocampus). Additionally, dual label light and electron microscopic studies in select brain areas demonstrate that cell containing ERbeta-EGFP colocalize with both nuclear and extranuclear ERbeta-immunoreactivity. These findings support the utility of Esr2 BAC transgenic reporter mice for future studies understanding the role of ERbeta in CNS function.
Milner
Teresa A
TA
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, USA; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: tmilner@med.cornell.edu.
Thompson
Louisa I
LI
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, USA; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Wang
Gang
G
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, USA.
Kievits
Justin A
JA
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, USA.
Martin
Eugene
E
Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Zhou
Ping
P
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, USA.
McEwen
Bruce S
BS
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Pfaff
Donald W
DW
Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Waters
Elizabeth M
EM
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D017207:Rats, Sprague-Dawley
D047629:Estrogen Receptor beta