Form 3
Report for Joint/Usage Research Program for Endocrine/Metabolism(Fiscal Year 2022)
Date：2023/04/03

To Director of Institute for Molecular and Cellular Regulation, Gunma University
Principal Applicant
Institution

Faculty of Medicine Siriraj Hospital, Mahidol University

Position

Instructor-Head of Cellular and Molecular Diabetes ResearchGroup

Name

Prapaporn Thamtarana

We report on the results of joint research in fiscal 2022 as below.
（Program No. 2022-3-3）

１．Research Title

Characterization of Dnajc3, a candidate gene for autosomal dominant diabetes

２．Purpose andSignificance of theresearch project

Functional characterization of novel autosomal dominant diabetes associatedgene Dnajc3 in human pancreatic alpha cells and beta cells.

３．Period of The Program

April 1, 2022 ～ March 31, 2023

４．Project Members
Name

Age

Sex

Affiliation

41

F

Mahidol University/
Faculty of Medicine Siriraj Hospital/Research Department

Position

Role（Principal Applicant）

Prapaporn
Thamtarana

Instructor

Project director（Research Collaborators）

Pa-thai
Yenchitsomanus

Mahidol University/
Faculty of Medicine Siriraj HosProfessor
pital/Research Department
Mahidol University/
Nattachet
Associate Pro58
M Faculty of Medicine Siriraj HosPlengvidhya
fessorpital/Department of Medicine
Mahidol University/
Chutima
Research Assis41
F Faculty of Medicine Siriraj HosChanprasert
tantpital/Research Department
Mahidol University/
Research AssisSiriporn
31
F Faculty of Medicine Siriraj HostantRiyajanpital/Research Department※If additional space is required, please attach a separate sheet.
５．Collaborating Researcher Name ofDiabetes andNameof IMCR
Laboratory
Metabolic Disorders
69

M

1 / 2

Consultant
Clinician/Subject
recruitment
Genetic and Genomic analyses
Cell analysis

JunShirakawa

Institute for Molecular andCellular Regulation IMCR
Gunma University６． Research Plans
Monogenic diabetes is a heterogeneous group of distinct subtypes of diabetes characterized by different
modes of inheritance and age of onset. Familial diabetes with autosomal dominant inheritance is morecommon and has more variable age of onset. Maturity-onset diabetes of the young (MODY) is a form ofautosomal dominant diabetes that generally occurs during childhood and adolescence. Mutations in at least
fourteen different genes (MODY1-MODY14) have been described to date as the cause of MODY in different families. However, in Asian populations, such as Chinese, Japanese, Korean, and Thai, up to 85% of
MODY cases have unknown genetic causes.
We previously identified a missense mutation (c.T1424C:p.L475P) in ZYG11A identified by exome sequencing as segregating with hyperglycemia in a Thai family with autosomal dominant diabetes. ZYG11A
functions as a target recruitment subunit of an E3 ubiquitin ligase complex that plays an important role in
the regulation of cell cycle. We recently reported that ZYG11A as a cell cycle regulator required for beta-cellgrowth (Mol Cell Endocrinol. 2021) by this Joint/Usage Research Program for Endocrine/Metabolism in
2021.
We also identified a mutation in Dnajc3 identified by exome sequencing as segregating with hyperglycemia
in a Thai family with autosomal dominant diabetes. Dnajc3 is a chaperon protein involved in protein foldingand ER stress. In this study, the role of Dnajc3 in beta cells are evaluated.
７．Research results:
Please describe the details of the contribution of the joint research with IMCR in obtaining the results.
We analyzed the expression of Dnajc3 in islets under ER stress and found the time-dependent alteration ofthat expression.
Overexpression of WT and mutant Dnajc3 was performed by transducing adenoviral vectors. Proteintranslation by polysome profiling and gene expression by qPCR were conducted in those cells. The role ofDnsjc3 in the regulation of ER stress was estimated in terms of human mutation.

８．Present status of academic conference presentations and research papers associated with the resultsof the joint research, and exchange of information on the joint research with the collaborating researcher at
IMCR.
(As much as possible, please state papers that include the names of the collaborating researcher at IMCRor papers stating that the research was supported by the Joint Research Program with IMCR.
Regarding papers, please send a PDF file together with the report to the email address of the general affairs section of the Institute.) Office of General Affairs: kk-msomu4@jimu.gunma-u.ac.jp① Please list the publications that include the name of the collaborating researcher from IMCR and send areprint of each publication to IMCR.

We are preparing the collaborative paper.
② Please list the publications that include a description that the research was supported by the JointN/A③N/A

Research Program with IMCR and send a reprint of each publication to IMCR.

List up to 3 conferences (name of conference, date of conference, and title of the presentation).

Exchange of information exchange with collaborating researcher from IMCR (please list main points ofcommunication).
We usually have web meetings monthly to share the experimental results.

④2 / 2

Institute for Molecular andCellular Regulation IMCR
Gunma University