The present invention relates in one aspect to a method of making a knock-out mouse having its lambda light chain locus C2-C4-C3-C1 deleted using LoxP constructs as the targeting constructs and ubiquitous Cre-expresser mice. Also provided is a method of making a double knock-out mouse that has both the lambda light chain and the kappa light chain loci deleted. A heavy chain only antibody produced in a mouse in which at least the lambda light chain locus is functionally silenced is a further aspect of the invention.