Disclosed is a method of producing a mouse cell comprising a genome that comprises a functional polynucleotide sequence that encodes a chimeric immunoglobulin heavy chain that functionally replaces an endogenous immunoglobulin heavy chain locus, wherein said chimeric immunoglobulin heavy chain comprises a human variable domain and a chimeric constant region, said method comprising the steps of: designing a DNA construct in silico, wherein said construct comprises one or more unrearranged human V, D and/or J gene segments, a human CH1 gene segment, a human upper hinge region gene segment, a mouse CH2 gene segment, and a mouse CH3 gene segment； producing said one or more DNA constructs； and introducing the one or more constructs into the genome of a cell. Further disclosed is a mouse cell as per the method as disclosed above or a mouse contain said cell.
