Abstract: A method for preparing a non-human mammal or progeny thereof, and the use thereof. The preparation method includes making a CH1 domain of an IgM heavy chain constant region not expressed or incorrectly expressed in the non-human mammal; and making one, two, three, four or more genes encoding an IgG heavy chain constant region in the non-human mammal not express or incorrectly express a CH1 domain during expression. The obtained non-human mammal or progeny thereof can be used for preparing a heavy chain antibody. The non-human mammal obtained by using the preparation method of the present application does not introduce any exogenous gene encoding heavy chain variable and constant regions of an antibody, and can directly use all VDJ genes encoding the heavy chain variable region of the antibody in its own genome, so as to produce more diverse heavy chain antibodies.