his.sePublications
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A zebrafish model system for drug screening in diabetes
University of Skövde, School of Bioscience. Uppsala University, Department of Immunology, genetics and pathology.
2019 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

GWAS (Genome wide association studies) have aided in the discovery of various novel variants associated with diabetes. However, a detailed study is required to uncover the role of these genes and to determine how their dysfunction affects pathophysiology. Previous work in the lab has been successful in establishing zebrafish as an efficient model to characterise the effects of these candidate genes. Consequently, efforts have been also made to establish zebrafish as an efficient model system for drug screening as well. The current POP (Proof of principle) study aims to find whether treatment with tolbutamide drug in zebrafish carrying MODY (Maturity onset diabetes of the young) mutations has the similar effects in humans. The study employed zebrafish carrying five (gck, hnf1a, hnf1ba, hnf1bb, pdx1) CRISPR induced MODY orthologues. The zebrafish larvae were supplemented with tolbutamide drug from 5dpf till 10dpf (day post fertilisation). At 10dpf, larvae were screened for various glycaemic traits, whole body glucose and lipids as well body size. CRISPR-CAS9- induced mutations were quantified using paired end sequencing. The results showed that treatment with tolbutamide had a significant effect on the hyperglycaemic outcome induced by hnf1bb, hnf1a, and pdx1 mutations which was in line with the known effects of the drug in humans. In conclusion, the POP study proved to be successful in leveraging zebrafish as an efficient model system for, in vivo characterisation of drugs and can likely help to identify novel targets for therapeutic interventions.

Place, publisher, year, edition, pages
2019. , p. 41
Keywords [en]
Zebrafish, CRISPR-Cas9, Diabetes Mellitus, GWAS
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:his:diva-17847OAI: oai:DiVA.org:his-17847DiVA, id: diva2:1367671
Subject / course
Systems Biology
Educational program
Systems Biology - Master’s Programme
Supervisors
Examiners
Available from: 2019-11-06 Created: 2019-11-04 Last updated: 2019-11-06Bibliographically approved

Open Access in DiVA

fulltext(911 kB)16 downloads
File information
File name FULLTEXT01.pdfFile size 911 kBChecksum SHA-512
fff45357c8c53063697b5faefe9fead02ca61200d0d5a4ac7e393f05b948aee4d63b939d2cdaba2bbd66ff89c7a69ce4dac9e12df86f8afd9ab428753fdddf15
Type fulltextMimetype application/pdf

By organisation
School of Bioscience
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 16 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

urn-nbn

Altmetric score

urn-nbn
Total: 66 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf