Abstract: Nucleic acid molecules include immunoglobulin genes or parts of immunoglobulin genes. The nucleic acid molecules includes the IgM gene (IgHC?) and IgM switch region (S?). The sequences of the S? and the IgHC? are both derived from a transgenic host animal. In this invention, human antibodies are directly generated and no humanization process is required, and the human antibody druggability is increased. The transgenic human antibody mouse has normal early B?cell development, maturation and the B?cell number in comparison with that of wild type animal, thereby facilitating the differentiation of the B?cells. The specificity and diversity of the produced antibody are improved; and the efficiency for screening the therapeutic antibody is improved.

Abstract: Nucleic acid molecules and single-domain antibody applications are provided. The nucleic acid molecules include a transgenic host animal immunoglobulin genes or parts of immunoglobulin genes. Main characters are: it comprises the transgenic host animal IgH 5?-enhancer, IgM switch region (S?), and IgM sequences, specifically, all the IgM sequences are originated from the transgenic host animal, and the CH1 sequences of the IgM is deleted (IgM-dCH1). The regulatory control sequences of IgG are also derived from the transgenic host animal including S?, TM1, TM2, PolyA sequences, etc., and IgG C? sequences (Hinge, CH2 and CH3) are human sequence (Ig?-dCH1). The present invention ensures normal B-cell development in transgenic animal, and the transgenic animal expresses human single-domain antibodies, reducing the subsequent antibody humanization process and improving the druggability of the antibodies.

Abstract: Nucleic acid molecules include immunoglobulin genes or parts of immunoglobulin genes. The nucleic acid molecules includes the IgM gene (IgHC?) and IgM switch region (S?). The sequences of the S? and the IgHC? are both derived from a transgenic host animal. In this invention, human antibodies are directly generated and no humanization process is required, and the human antibody druggability is increased. The transgenic human antibody mouse has normal early B?cell development, maturation and the B?cell number in comparison with that of wild type animal, thereby facilitating the differentiation of the B?cells. The specificity and diversity of the produced antibody are improved; and the efficiency for screening the therapeutic antibody is improved.