A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region
A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region
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DOI：
10.1093/hmg/5.9.1305
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发表时间：
1996-09-01
影响因子：
3.5
通讯作者：
Pritchard, MA
中科院分区：
文献类型：
--
作者：
Guimera, J;Casas, C;Pritchard, MA
果蝇的minibrain（mnb）基因编码丝氨酸-苏氨酸蛋白激酶，在胚后神经发生中起重要作用。一个与mnb功能相似的相应人类基因可以为研究大脑的正常发育以及在许多先天性疾病中观察到的异常大脑发育和智力低下提供重要的见解。21三体或唐氏综合征（DS）是最常见的人类出生缺陷。它与精神发育迟滞和广泛的身体异常有关，人类21号染色体上的一个区域已被指定为唐氏综合征关键区（DSCR），当以三个拷贝存在时，这是导致DS的许多特征性特征的原因，包括精神发育迟滞。我们已经从DSCR中分离出mnb的人类同源物，MNB编码一个6.1 kb的转录本，在胎脑、肺、肾和肝中表达。使用人类探针，两个主要的转录本（6.1和3.1kb），并在小鼠脑的几个区域原位检测到表达，包括嗅球、小脑、大脑皮层、海马的锥体细胞层和几个下丘脑核，这种表达模式对应于DS患者大脑中异常的区域，并表明MNB的过度表达可能对DS患者产生不利影响。
The minibrain (mnb) gene of Drosophila melanogaster encodes a serine-threonine protein kinase with an essential role in postembryonic neurogenesis. A corresponding human gene with similar function to mnb could provide important insights into both normal brain development and the abnormal brain development and mental retardation observed in many congenital disorders. Trisomy 21 or Down syndrome (DS) is the most frequent human birth defect. It is associated with mental retardation and a broad spectrum of physical abnormalities, A region on human chromosome 21 has been designated the Down syndrome critical region (DSCR) and when present in three copies, this is responsible for many of the characteristic features of DS, including mental retardation, We have isolated a human homologue of mnb from the DSCR, MNB encodes a 6.1 kb transcript which is expressed in foetal brain, lung, kidney and liver. Using a human probe, two major transcripts (6.1 and 3.1 kb) were identified in mouse and expression was detected in situ in several regions of the mouse brain, including the olfactory bulb, the cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and several hypothalamic nuclei, This expression pattern corresponds to the regions of the brain that are abnormal in individuals with DS and suggests that overexpression of MNB could have detrimental consequences in DS patients.