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| Status |
Public on Feb 14, 2015 |
| Title |
Reduced insulin secretion in WFS1-deficient mice may be related to downregulation of Trpm5 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the WFS1 gene. WFS1 encodes an endoplasmic reticulum resident transmembrane protein. The Wfs1-null mice exhibit progressive insulin deficiency and diabetes. The aim of the present study was to describe the insulin secretion and transcriptome of pancreatic islets in WFS1-deficient mice. WFS1-deficient (Wfs1KO) mice had considerably less pancreatic islets than heterozygous (Wfs1HZ) or wild-type (WT) mice. Wfs1KO pancreatic islets secreted less insulin after stimulation with 2 and 10 mM glucose and with tolbutamide solution compared to WT and Wfs1HZ islets, but not after stimulation with 20 mM glucose. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KO had an increased level of proinsulin. After stimulation with 2 mM glucose solution the proinsulin/insulin ratio in Wfs1KO was significantly higher than that of WT and Wfs1HZ. RNA-seq from pancreatic islets found melastatin-related transient receptor potential subfamily member 5 protein gene (Trpm5) to be downregulated in WFS1-deficient mice. Functional annotation of RNA sequencing results showed that WFS1 deficiency influenced significantly the pathways related to tissue morphology, endocrine system development and function, molecular transport network. These findings suggest an interactive role of WFS1 and TRPM5 in insulin secretion.
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| Overall design |
12 samples: three genotypes, 4 individuals in each genotype
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| Contributor(s) |
Ivask M, Hugill A, Plaas M, Kõks S |
| Citation(s) |
27053292 |
| |
| Submission date |
Feb 13, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Sulev Koks |
| E-mail(s) |
sulev.koks@murdoch.edu.au
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| Phone |
+61864570313
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| Organization name |
Murdoch University
|
| Department |
Centre for Molecular Medicine and Innovative Therapeutics
|
| Street address |
90 South Street
|
| City |
Perth |
| State/province |
Western Australia |
| ZIP/Postal code |
6150 |
| Country |
Australia |
| |
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| Platforms (1) |
| GPL15907 |
AB 5500xl Genetic Analyzer (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA275429 |
| SRA |
SRP055028 |
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