Forsøksdyr: Investigating the enteric nervous system development in mice

Godkjenningsdato 26.10.2018

Godkjenningsperiode 26.10.2018-25.10.2022

I . The aim of the project is to study how epigenetics influence the development of enteric neural crest derived cells (NCCs) in the context of enteric nervous system development in the mice embryo. We will use a transgenic, inducible reporter mice model SOX10/eYFP. This will allow us to track this cells and isolate them for further characterization. We will harvest the GI tract from embryos at different time points during development and early postnatal period. We will perform epigenetic analysis on the DNA/RNA from these samples.
II. Reports from other laboratories using the same reporter mice line do not include any adverse effects related to the genotype. Life expectancy and phenotype is normal. The animals will only experience a mild distress when handled and marked for genotyping. They will also experience a mild distress when injected with 4-hydroxytamoxifen to induce expression of the reporter. We will study embryos as well as isolate cells from the guts of those embryos at different stages. We will also harvest tissues from 1 week old postnatal animals and thus have a full panorama of the dynamics of the development of the enteric nervous system.
III. A failure in the normal development of the enteric nervous system results in human disease. Among these diseases, Hirschsprung’s disease is a congenital disease that affects newborns. Current treatment involves radical surgery, although complications and long term motility issues are common. This project will allow us to gain more understanding of this disease, and open avenues for new potential sources of treatment.
IV. We would like to use around 315 adult mice and embryos (mus musculus), C57BL/6.
V. In order to reduce the waste of animals, we will use some of the wild type mice generated during the breeding for breeding in other of the mice lines the group maintains.