Wenke Jonas, Oliver Kluth, Anett Helms, Sarah Voss, Markus Jahnert, Pascal Gottmann, Thilo Speckmann, Birgit Knebel, Alexandra Chadt, Hadi Al-Hasani, Annette Schürmann, Heike Vogel
- Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options.
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls.
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis.
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified theCurrent attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options.
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls.
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis.
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.…
MetadatenAuthor details: | Wenke JonasGND, Oliver Kluth, Anett Helms, Sarah Voss, Markus JahnertORCiD, Pascal GottmannORCiD, Thilo SpeckmannORCiD, Birgit KnebelORCiD, Alexandra ChadtORCiDGND, Hadi Al-HasaniGND, Annette SchürmannORCiDGND, Heike VogelORCiDGND |
---|
DOI: | https://doi.org/10.3390/ijms23063205 |
---|
ISSN: | 1661-6596 |
---|
ISSN: | 1422-0067 |
---|
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/35328627 |
---|
Title of parent work (English): | International journal of molecular sciences |
---|
Publisher: | MDPI |
---|
Place of publishing: | Basel |
---|
Publication type: | Article |
---|
Language: | English |
---|
Date of first publication: | 2022/03/16 |
---|
Publication year: | 2022 |
---|
Release date: | 2024/04/12 |
---|
Tag: | QTL; apoptosis; beta-cell; diabetes; proliferation |
---|
Volume: | 23 |
---|
Issue: | 6 |
---|
Article number: | 3205 |
---|
Number of pages: | 13 |
---|
Funding institution: | German Ministry of Education and Research and the State of Brandenburg; [82DZD00302]; Deutsche Forschungsgemeinschaft (DFG, German Research; Foundation) [491394008] |
---|
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
---|
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
---|
| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Peer review: | Referiert |
---|
Publishing method: | Open Access / Gold Open-Access |
---|
| DOAJ gelistet |
---|
License (German): | CC-BY - Namensnennung 4.0 International |
---|