Genetically modified non-human mammals and cells
A genetically modified mouse characterized 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 or mouse cell characterised in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide 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.
2. A genetically modified mouse or mouse cell according to claim 1 characterised in that all the endogenous Ig H Variable region, D and J segment nucleic acid sequences are present.
3. A genetically modified mouse or mouse cell according to claim 1 characterised in that it does not comprise a nucleic acid sequence which itself encodes any immunoglobulin heavy chain constant region (IgH C) polypeptide.
4. A genetically modified mouse or mouse cell according to claim 1 characterised in that all immunoglobulin heavy chain constant region gene sequences are absent or partially absent from the genome.
5. A genetically modified mouse or mouse cell according to claim 1 characterised in that it is obtainable or obtained by targeted deletion of essentially all endogenous IgH C gene sequences.
6. A genetically modified mouse or mouse cell according to claim 1 characterised in that it is obtainable or obtained by Cre loxP recombination.
7. A genetically modified mouse or mouse cell according to claim 1 characterised in that at least part of at least one IgH C gene enhancer sequence is present.
8. A genetically modified mouse or mouse cell according to claim 1 characterised in that a non-endogenous site-specific recombination sequence is present within the genome.
9. A genetically modified mouse or mouse cell according to claim 1 characterised in that all eight endogenous IgH C genes μ, δ, γ3, γ1, γ2a, γ2b, ε and α are absent or partially absent.
10. A genetically modified mouse cell according to claim 1 characterised in that it is an embryonic stem cell.
11. A genetically modified mouse or mouse cell derived from a genetically modified mouse or mouse cell of claim 1 .