Genetically modified non-human mammals and cells
A genetically modified non-human mammal or cell characterised in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide.
1. A genetically modified mouse characterised in that the complete coding region of the endogenous immunoglobulin heavy chain constant region locus is deleted and in that one or more endogenous Ig H Variable region, one or more endogenous Ig H D segment, and one or more endogenous Ig H J segment nucleic acid sequences are present and characterised in that the genetically modified mouse does not comprise a nucleic acid sequence which itself encodes any immunoglobulin heavy chain constant region (IgH C) polypeptide.
2. A genetically modified mouse according to claim 1 , wherein all the endogenous Ig H Variable region, D and J segment nucleic acid sequences are present.
3. A genetically modified mouse according to claim 1 , characterised in that it is obtainable or obtained by targeted deletion of all endogenous IgH C gene sequences.
4. A genetically modified mouse according to claim 1 characterised in that it is obtainable or obtained by Cre loxP recombination.
5. A genetically modified mouse according to claim 1 characterised in that at least part of at least one IgH C gene enhancer sequence is present.
6. A genetically modified mouse according to claim 1 characterised in that a non-endogenous site-specific recombination sequence is present within the genome.
7. A genetically modified mouse according to claim 1 characterised in that one or more selectable marker(s) is present within the genome.
8. A genetically modified mouse according to claim 6 characterised in that at least one selectable marker is present upstream of, or downstream of, the non-endogenous site specific recombination sequence.
9. A genetically modified mouse according to claim 7 characterised in that the selectable marker(s) is one or more selectable marker selected from a group comprising a neomycin resistance gene, a puromycin resistance gene, and a hygromycin resistance gene.
10. A genetically modified mouse according to claim 6 characterised in that the non-endogenous site-specific recombination sequence is a loxP site.
11. A genetically modified mouse derived from a genetically modified mouse of claim 1 .
12. A genetically modified mouse cell obtained from a genetically modified mouse of claim 1 .
13. A genetically modified mouse cell according to claim 12 characterised in that it is an embryonic stem cell.
14. A genetically modified mouse cell obtained from a genetically modified mouse of claim 2 .
15. A genetically modified mouse cell obtained from a genetically modified mouse of claim 3 .
16. A genetically modified mouse cell obtained from a genetically modified mouse of claim 4 .
17. A genetically modified mouse cell obtained from a genetically modified mouse of claim 5 .
18. A genetically modified mouse cell obtained from a genetically modified mouse of claim 6 .
19. A genetically modified mouse cell obtained from a genetically modified mouse of claim 7 .
20. A genetically modified mouse cell obtained from a genetically modified mouse of claim 8 .
21. A genetically modified mouse cell obtained from a genetically modified mouse of claim 9 .
22. A genetically modified mouse cell obtained from a genetically modified mouse of claim 10 .