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小鼠载脂蛋白D基因的分子克隆及其在C型尼曼-匹克病小鼠模型中的上调表达。

Molecular cloning of the mouse apolipoprotein D gene and its upregulated expression in Niemann-Pick disease type C mouse model.

作者信息

Yoshida K, Cleaveland E S, Nagle J W, French S, Yaswen L, Ohshima T, Brady R O, Pentchev P G, Kulkarni A B

机构信息

Gene Targeting Research and Core Facility, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

DNA Cell Biol. 1996 Oct;15(10):873-82. doi: 10.1089/dna.1996.15.873.

DOI:10.1089/dna.1996.15.873
PMID:8892759
Abstract

Apolipoprotein D (ApoD) is a member of the lipocalin superfamily. The primary structure and diverse expression of ApoD suggest that this protein is a multiligand, multifunctional glycoprotein. Here we report the structure of the mouse ApoD gene, which is composed of six exons spanning approximately 20 kb in length. All the exon-intron splice junctions follow the consensus GT/AG sequence. The 5'-flanking region of the mouse ApoD gene contains several putative regulatory elements, including FSE-2, GRE, SDR, MRE, IL-6RE, and TATA box. Northern blot analysis revealed that ApoD was highly expressed in the brain and adipose tissue in mouse. Lower levels of expression were observed in the heart, lung, thymus, testis, and salivary glands. In situ hybridization for the brain showed that ApoD mRNA was mainly localized in the subarachnoid space including the pia. In the Niemann-Pick disease type C mouse model, ApoD expression was upregulated in many organs such as brain, adipose tissue, heart, and thymus, presumably due to enhanced ApoD synthesis in perivascular fibroblasts.

摘要

载脂蛋白D(ApoD)是脂质运载蛋白超家族的成员。ApoD的一级结构和多样的表达表明该蛋白是一种多配体、多功能糖蛋白。在此我们报道小鼠ApoD基因的结构,它由六个外显子组成,长度约为20 kb。所有外显子-内含子剪接位点均遵循一致的GT/AG序列。小鼠ApoD基因的5'侧翼区包含几个假定的调控元件,包括FSE-2、GRE、SDR、MRE、IL-6RE和TATA盒。Northern印迹分析显示,ApoD在小鼠的脑和脂肪组织中高表达。在心脏、肺、胸腺、睾丸和唾液腺中观察到较低水平的表达。对脑进行原位杂交显示,ApoD mRNA主要定位于包括软脑膜在内的蛛网膜下腔。在尼曼-匹克病C型小鼠模型中,ApoD在许多器官如脑、脂肪组织、心脏和胸腺中表达上调,推测这是由于血管周围成纤维细胞中ApoD合成增强所致。

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