Tian Qi, Smart James L, Clement Joachim H, Wang Yingming, Derkatch Alex, Schubert Harald, Danilchik Michael V, Marks Daniel L, Fedorov Lev M
OHSU Transgenic Mouse Models Shared Resource, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
George Fox University, Newberg, OR, USA.
Histochem Cell Biol. 2016 May;145(5):561-72. doi: 10.1007/s00418-015-1394-3. Epub 2015 Dec 26.
Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expression pattern of RHEB1 was analyzed in both embryonic (at E3.5-E16.5) and adult (1-month old) mice. RHEB1 immunostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These independent methods revealed similar RHEB1 expression patterns during both embryonic and postnatal developments. Ubiquitous uniform RHEB1/β-gal and/or RHEB1 expression was seen in preimplantation embryos at E3.5 and postimplantation embryos up to E12.5. Between stages E13.5 and E16.5, RHEB1 expression levels became complex: In particular, strong expression was identified in neural tissues, including the neuroepithelial layer of the mesencephalon, telencephalon, and neural tube of CNS and dorsal root ganglia. In addition, strong expression was seen in certain peripheral tissues including heart, intestine, muscle, and urinary bladder. Postnatal mice have broad spatial RHEB1 expression in different regions of the cerebral cortex, subcortical regions (including hippocampus), olfactory bulb, medulla oblongata, and cerebellum (particularly in Purkinje cells). Significant RHEB1 expression was also viewed in internal organs including the heart, intestine, urinary bladder, and muscle. Moreover, adult animals have complex tissue- and organ-specific RHEB1 expression patterns with different intensities observed throughout postnatal development. Its expression level is in general comparable in CNS and other organs of mouse. Thus, the expression pattern of RHEB1 suggests that it likely plays a ubiquitous role in the development of the early embryo with more tissue-specific roles in later development.
富含脑的Ras同源物（RHEB1）是由RAS癌基因编码的GTP结合蛋白超家族中的一员。RHEB1位于包括胰岛素信号通路在内的几条重要通路的交叉点，因此在不同的生理过程中发挥重要作用。为了更好地理解RHEB1蛋白的生理相关性，我们分析了RHEB1在胚胎期（E3.5-E16.5）和成年期（1月龄）小鼠中的表达模式。分别对野生型和Rheb1基因陷阱突变小鼠进行了RHEB1免疫染色和X-gal染色。这些独立的方法揭示了胚胎期和出生后发育过程中相似的RHEB1表达模式。在E3.5的植入前胚胎和直至E12.5的植入后胚胎中均可见普遍均匀的RHEB1/β-半乳糖苷酶和/或RHEB1表达。在E13.5和E16.5阶段之间，RHEB1表达水平变得复杂：特别是在神经组织中发现了强表达，包括中脑、端脑的神经上皮层、中枢神经系统的神经管和背根神经节。此外，在某些外周组织如心脏、肠道、肌肉和膀胱中也观察到强表达。出生后的小鼠在大脑皮层、皮层下区域（包括海马体）、嗅球、延髓和小脑（特别是浦肯野细胞）的不同区域具有广泛的空间RHEB1表达。在包括心脏、肠道、膀胱和肌肉在内的内脏器官中也观察到显著的RHEB1表达。此外，成年动物具有复杂的组织和器官特异性RHEB1表达模式，在出生后的发育过程中观察到不同的强度。其表达水平在小鼠的中枢神经系统和其他器官中总体相当。因此，RHEB1的表达模式表明它可能在早期胚胎发育中发挥普遍作用，而在后期发育中发挥更多组织特异性作用。
