Abstract
The human DNAJB3 gene encodes a DNAJ (Heat shock protein 40; Hsp40) homolog, subfamily B, member 3 chaperone protein (DNAJB3), which can be down-regulated in disease conditions, as observed in decreased expression of DNAJB3 mRNA in peripheral blood mononuclear cells (PBMC) of obese patients. Recently, humanized UDP-glucuronosyltransferase (UGT) 1 mice (hUGT1 mice) were developed, in which the introduced human UGT1 gene contained a gene encoding human DNAJB3. In the present study, we analyzed the expression of human DNAJB3 mRNA in hUGT1 mice. Among the examined tissues, the testis had the highest expression of human DNAJB3 mRNA, while the lowest expression was observed in the liver. We found that the pattern of tissue-specific expression of mouse Dnajb3 in hUGT1 mice was very similar to that of human DNAJB3. We further demonstrated that the expression of human DNAJB3 in the liver was significantly reduced in high-fat-diet-fed hUGT1 mice compared to the expression level in the control mice, indicating that the expression of human DNAJB3 in hUGT1 mice could be similarly regulated in disease conditions such as obesity. Humanized UGT1 mice might therefore be useful to investigate the physiological role of human DNAJB3 in vivo.
Highlights
Heat shock proteins (HSPs) were originally defined as a group of proteins induced by heat shock [1].HSPs are widely recognized as cellular proteins that can be induced under various stress conditions such as hypoxia and virus infection [2,3]
While the humanized UGT1 (hUGT1) mice were remarkably useful in the fields of drug metabolism and pharmacokinetics, it was further discovered that the human UGT1 transgene, which was introduced in the hUGT1 mice, contained a gene encoding DNAJB3 (Figure 1)
DNAJB3 mRNA was expressed in hUGT1 mice and that primers specific to human DNAJB3 could amplify the corresponding fragments
Summary
Heat shock proteins (HSPs) were originally defined as a group of proteins induced by heat shock [1]. While the basic function of HSP includes regulation of cell growth, apoptosis, and protein homeostasis [2], recent studies have shown that various. 41 DNAJ member proteins are classified into three families, DNAJA, DNAJB, and DNAJC, which contain 6, 12, and 23 members, respectively. While DNAJB1 is not induced by heat shock [6], a recent study demonstrated that DNAJB3 was down-regulated in disease conditions, as decreased expression of DNAJB3 mRNA was observed in peripheral blood mononuclear cells (PBMC) of obese patients. While the hUGT1 mice were remarkably useful in the fields of drug metabolism and pharmacokinetics, it was further discovered that the human UGT1 transgene, which was introduced in the hUGT1 mice, contained a gene encoding DNAJB3 (Figure 1). We analyzed the expression of human DNAJB3 mRNA in hUGT1 mice.
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