Forsøksdyr: Colony breeding and characterisation of the humanized integrin alpha11 mice (hITGA11 KI strain)

Godkjenningsdato 14.08.2020

Godkjenningsperiode 14.08.2020-14.08.2023

1 Purpose
In this application, we apply to import the newly-generated hITGA11 KI mice (F1) for further breeding, backcrossing and characterisation. These mice will be further used to test the human integrin alpha11 blocking antibodies in different animal models involving integrin alpha11. The respective experiment will be planned afterwards together with collaborative groups and a separate application will be sent in when it’s needed.

2 Distress
In the strategy to generate the hITGA11 KI mice, the human integrin alpha11 (ITGA11) cDNA was inserted to the exon of mouse integrin alpha11 gene (Itga11), and thus inactivate Itga11 and replace it with expression of ITGA11. Since there is a high degree of sequence homology (90% identity) and function similarity (based on our previous studies) between human and mouse integrin alpha11 proteins, we do NOT expect to have any phenotype in these humanized mice.

3 Expected benefit
Once the hITGA11 KI mice are characterized and the mouse strain is successfully established, this will be the first humanized mouse strain for integrin alpha11. This mouse strain is necessary to be used to test the newly-developed human integrin alpha11 antibodies in vivo since the antibodies do not cross-react with mouse integrin alpha11, which will give important information in assessing the potential usage of the antibodies in the diagnosis and treatment of human fibrotic diseases or tumorigenesis where involvement of integrin alpha11 has been indicated.

4 Number of animals, and what kind
hITGA11 KI mice F1 and backcrossed offspring: 300
C57BL/6J wildtype mice and inbred offspring: 240

5 How to adhere to 3R
- Replacement: This mouse strain is necessary to have when testing the human integrin alpha11 antibodies in vivo since the antibodies do not cross-react with mouse integrin alpha11.
- Reduction: we will backcross the F1 mice as soon as possible (for at least 5 generations) while using minimum number of mice. We will also cooperate the breeding with characterisation and try to make full use of the mouse offspring and embryos to analyse the expression pattern of human integrin alpha11 in different tissues or embryonic stages.
- Refinement: Backcrossing, genotyping and tissue analyses will be performed cooperatively. Further experiments based on the established strain will be planned ahead and the mouse colony size will be adjusted and kept in minimum. Corresponding experiment application will be sent when it is needed.