IDENTIFICATION AND CHARACTERIZATION OF A 2ND MOUSE NRAMP GENE

IDENTIFICATION AND CHARACTERIZATION OF A 2ND MOUSE NRAMP GENE
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DOI:
10.1016/0888-7543(95)80053-o
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发表时间:
1995-01-20
期刊:
影响因子:
4.4
通讯作者:
GROS, P
GROS, P
中科院分区:
生物学3区
文献类型:
--
作者:
GRUENHEID, S;CELLIER, M;GROS, P

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Nramp基因作为宿主抗性基因座Bcg/Ity/Lsh的候选基因被分离,该基因座控制小鼠对几种类型感染的天然抗性。我们已经通过交叉杂交分离了对应于第二个小鼠Nramp基因的cDNA克隆,我们将其命名为Nramp 2。Nramp 2全长cDNA克隆的核苷酸和预测的氨基酸序列分析表明,这种新的Nramp蛋白与先前描述的Nramp密切同源,并且这两个基因形成一个小基因家族的一部分。这两个Nramp蛋白编码的整合膜蛋白共享63%的相同残基和78%的总体同源性。它们具有非常相似的二级结构,包括相同的亲水性特征和预测的膜组织,具有至少10个且最可能12个跨膜结构域,一簇预测的N-连接糖基化位点和一个共有转运基序。通过北方印迹分析Nramp 2 mRNA转录物在正常小鼠组织中的分布,发现Nramp 2基因产生几种mRNA,包括通过使用替代聚腺苷酸化信号产生的突出的3.3-和2.3-kb种类。与先前描述的巨噬细胞特异性Nramp基因相反,发现Nramp 2 mRNA在所有测试组织中以低水平表达。使用在mRNA的3'非翻译区鉴定的多态性(GT)(26)二核苷酸重复,我们将Nramp 2基因定位于小鼠15号染色体的远端部分标记D15 Mit 41和D15 Mit 15之间,基因顺序和基因间距离(cM)为:着丝粒-56.1-D15 Mit 41-(1 +/- 1)-Nramp 2-(5 +/- 2)-D15 Mit 15。(C)出版社:Academic Press
The Nramp gene was isolated as a candidate for the host resistance locus Bcg/Ity/Lsh, which controls natural resistance of mice to several types of infections. We have isolated by cross-hybridization cDNA clones corresponding to a second mouse Nramp gene, which we designate Nramp2. Nucleotide and predicted amino acid sequence analyses of full-length cDNA clones for Nramp2 indicate that this novel Nramp protein is closely homologous to the previously described Nramp and that the two genes form part of a small gene family. The two Nramp proteins encode integral membrane proteins that share 63% identical residues and an overall homology of 78%. They share very similar secondary structure, including identical hydropathy profiles and predicted membrane organization, with a minimum of 10 and most probably 12 transmembrane domains, a cluster of predicted N-linked glycosylation sites, and a consensus transport motif. Analysis of the distribution of Nramp2 mRNA transcripts in normal mouse tissues by Northern blotting revealed that the Nramp2 gene produces several mRNAs, including prominent 3.3- and 2.3-kb species generated by the use of alternative polyadenylation signals. In contrast to the previously described macrophage-specific Nramp gene, Nramp2 mRNAs were found to be expressed at low levels in all tissues tested. Using a polymorphic (GT)(26) dinucleotide repeat identified in the 3' untranslated region of the mRNA, we have mapped the Nramp2 gene to the distal part of mouse chromosome 15 between markers D15Mit41 and D15Mit15, with the gene order and intergene distance (in cM): centromere-56.1-D15Mit41-(1 +/- 1)-Nramp2-(5 +/- 2)-D15Mit15. (C) 1995 Academic Press, Inc.