Engineering mouse models to investigate the function of imprinting

Some insight into the developmental basis for imprinting specific genes during the evolution of mammals can be gained from conventional gene 'knockout' studies. However, the consequences of full loss of function are often wide-ranging and may obscure the critical, dosage-related phenotype. This review focuses on transgenic techniques employed to alter the dosage of imprinted genes, including the application of bacterial artificial chromosome transgenic mice, in imprinting research. Advantages of dosage-based techniques over conventional knockout studies will be discussed, with examples. Important applications of transgenic mice in imprinting research, including studying gene expression patterns, the identification of imprinting centres and isolating the consequences of altered gene dosage, are reviewed with a particular focus on the imprinted domain on mouse distal chromosome 7.