TY  - JOUR
A1  - Kluth, Oliver
A1  - Stadion, Mandy
A1  - Gottmann, Pascal
A1  - Aga-Barfknecht, Heja
A1  - Jähnert, Markus
A1  - Scherneck, Stephan
A1  - Vogel, Heike
A1  - Krus, Ulrika
A1  - Seelig, Anett
A1  - Ling, Charlotte
A1  - Gerdes, Jantje
A1  - Schürmann, Annette
T1  - Decreased expression of cilia genes in pancreatic islets as a risk factor for type 2 diabetes in mice and humans
JF  - Cell reports
N2  - An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice. Among 327 differentially expressed mouse cilia genes, 81 human orthologs are also affected in islets of diabetic donors. Islets of nondiabetic mice and humans show a substantial overlap of upregulated cilia genes that are linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impairs division of MINE beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. These findings demonstrate the substantial role of cilia-gene regulation on islet function and T2D risk.
Y1  - 2019
U6  - https://doi.org/10.1016/j.celrep.2019.02.056
SN  - 2211-1247
VL  - 26
IS  - 11
SP  - 3027
EP  - 3036
PB  - Cell Press
CY  - Maryland Heights
ER  - 
TY  - JOUR
A1  - Jonas, Wenke
A1  - Kluth, Oliver
A1  - Helms, Anett
A1  - Voss, Sarah
A1  - Jahnert, Markus
A1  - Gottmann, Pascal
A1  - Speckmann, Thilo
A1  - Knebel, Birgit
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel genes involved in hyperglycemia in mice
JF  - International journal of molecular sciences
N2  - 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 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.
KW  - beta-cell
KW  - diabetes
KW  - proliferation
KW  - apoptosis
KW  - QTL
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063205
SN  - 1661-6596
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
ER  -