There are three subtypes of alpha2 adrenoceptor, i.e., alpha2A, alpha2B, and alpha2C, mediating the specific effect of epinephrine and norepinephrine in various tissues by means of G protein-coupled signal transduction pathways. In an attempt to delineate the regulatory mechanism of the alpha2B receptor subtype (encoded by subtype gene Adra2b) expression in the central nervous system (CNS), we have established transgenic (Tg) mice lines in which the transgene (NN-lacZ) was composed of the promoter region of Adra2b (NcoI fragment, 4.7 kb immediately upstream from receptor coding region) and a reporter gene lacZ (encoding beta-galactosidase). The selective expression of alpha2B in brain as indexed by beta-galactosidase, under the direction of this promoter region, may be traced in situ by using X-gal staining. The expression pattern of Adra2b-NN-lacZ in CNS of Tg mice during development was examined. The temporal course of examination was from gestation day 9.5 (E9.5) to postnatal day 28 (P28). Significant X-gal staining was detected in the dorsal root ganglion and cranial nerves V and VII at E12.5. By E18.5, expression was noted in the cerebral cortex, anterior olfactory nucleus, hypothalamus, brainstem, and cerebellar Purkinje cells, among others, and persisted through postnatal development. Adra2b-NN-directed reporter expression was detected in the hippocampal dentate gyrus first at P4. The temporal course of expression up to P28 in this area is in accordance with the developmental profiles of granule neurons of dentate gyrus. From P7 on, transgene expression was detected in additional brain areas, including the septum and thalamus. The expression correlates well with the noradrenergic innervations as evidenced by colocalization by using tyrosine hydroxylase or dopamine-beta-hydroxylase immunocytochemistry.
Copyright 2002 Wiley-Liss, Inc.