his.sePublikationer
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
A zebrafish model system for drug screening in diabetes
Högskolan i Skövde, Institutionen för biovetenskap. Uppsala University, Department of Immunology, genetics and pathology.
2019 (Engelska)Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
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.

Ort, förlag, år, upplaga, sidor
2019. , s. 41
Nyckelord [en]
Zebrafish, CRISPR-Cas9, Diabetes Mellitus, GWAS
Nationell ämneskategori
Naturvetenskap
Identifikatorer
URN: urn:nbn:se:his:diva-17847OAI: oai:DiVA.org:his-17847DiVA, id: diva2:1367671
Ämne / kurs
Systembiologi
Utbildningsprogram
Systembiologi - masterprogram
Handledare
Examinatorer
Tillgänglig från: 2019-11-06 Skapad: 2019-11-04 Senast uppdaterad: 2019-11-06Bibliografiskt granskad

Open Access i DiVA

fulltext(911 kB)16 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 911 kBChecksumma SHA-512
fff45357c8c53063697b5faefe9fead02ca61200d0d5a4ac7e393f05b948aee4d63b939d2cdaba2bbd66ff89c7a69ce4dac9e12df86f8afd9ab428753fdddf15
Typ fulltextMimetyp application/pdf

Av organisationen
Institutionen för biovetenskap
Naturvetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 16 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 59 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf