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Molecular cloning of the mouse apolipoprotein D gene and its upregulated expression in Niemann-Pick disease type C
K Yoshida1, E S Cleaveland, J W Nagle
1Gene Targeting Research and Core Facility, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
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.