MOLECULAR-CLONING OF THE MOUSE APOLIPOPROTEIN-D GENE AND ITS UP-REGULATED EXPRESSION IN NIEMANN-PICK DISEASE TYPE-C MOUSE MODEL

Apolipoprotein D (ApoD) is a member of the lipocalin superfamily, The primary structure and diverse expression of ApoD suggest that this pro tein is a multiligand, multifuuctional glycoprotein, Here we report th e structure of the mouse ApoD gene, which is composed of six exons spa nning approximately 20 kb in length, All the exon-intron splice juncti ons follow the consensus GT/AG sequence, The 5'-flanking region of the mouse ApoD gene contains several putative regulatory elements, includ ing FSE-2, GRE, SDR, MRE, IL-6RE, and TATA box, Northern blot analysis revealed that ApoD was highly expressed in the brain and adipose tiss ue in mouse, Lower levels of expression were observed in the heart, lu ng, 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 mode l, ApoD expression was upregulated in many organs such as brain, adipo se tissue, heart, and thymus, presumably due to enhanced ApoD synthesi s in perivascular fibroblasts.