Expression of Human DNAJ (Heat Shock Protein-40) B3 in Humanized UDP-glucuronosyltransferase 1 Mice

Ryo Mitsugi1, Tomoo Itoh2, Ryoichi Fujiwara3

  • 1Department of Pharmaceutics, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan. pl12032@st2.pharm.kitasato-u.ac.jp.

Insights

Human DNAJB3 chaperone protein expression, crucial in obesity, was studied in humanized UGT1 mice. Researchers found its expression patterns mirrored human levels and decreased in the liver of mice fed high-fat diets, suggesting a model for disease research.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The DNAJB3 gene encodes a DNAJ (Heat shock protein 40; Hsp40) homolog, subfamily B, member 3 chaperone protein (DNAJB3).
  • DNAJB3 expression is down-regulated in disease states, such as obesity, evidenced by decreased DNAJB3 mRNA in peripheral blood mononuclear cells (PBMC).
  • Humanized UDP-glucuronosyltransferase (UGT) 1 mice (hUGT1 mice) carrying the human DNAJB3 gene were recently developed.

Purpose of the Study:

  • To analyze the tissue-specific expression of human DNAJB3 mRNA in hUGT1 mice.
  • To investigate whether human DNAJB3 expression in hUGT1 mice is regulated similarly to human disease conditions like obesity.

Main Methods:

  • Quantitative analysis of human DNAJB3 mRNA expression across various tissues in hUGT1 mice.
  • Comparison of human DNAJB3 mRNA expression in the liver of hUGT1 mice fed a standard diet versus a high-fat diet.

Main Results:

  • The highest expression of human DNAJB3 mRNA was observed in the testis, with the lowest in the liver of hUGT1 mice.
  • The tissue-specific expression pattern of mouse Dnajb3 in hUGT1 mice closely resembled that of human DNAJB3.
  • High-fat diet-fed hUGT1 mice exhibited significantly reduced human DNAJB3 mRNA expression in the liver compared to control mice.

Conclusions:

  • Human DNAJB3 expression in hUGT1 mice shows tissue-specific patterns similar to humans.
  • The regulation of human DNAJB3 expression in hUGT1 mice, particularly its reduction in the liver under high-fat diet conditions, mirrors disease-related changes observed in humans.
  • hUGT1 mice serve as a valuable in vivo model for studying the physiological role of human DNAJB3 and its involvement in disease states such as obesity.

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