#9 Transgenic Mice as Immunogenicity Model

  • Jan L Ottesen Dept. of Gene Technology and Virology, Novo Nordisk A/S


The development of antibodies after administration of pharmaceutical proteins is not only of academic interest. Antibodies can be responsible for local and systemic allergic reactions, injection site lipoatrophy and have effect on the dose requirements.Tolerant transgenic mice are used to evaluate the potential immunogenicity of pharmaceutical proteins, e.g.. human insulin. human tissue plasminogen activator and human growth hormone. The results indicate that transgenic mice should be useful as an in vivo model to map immunogenic epitopes. Transgenic mice with tissue specific expression of human insulin that are tolerant to human insulin (in contrast to their nontransgenic littermates that produce antibodies)
are able to respond with antibody formation against human insulin With substitution of single amino acids, if the substitutions results in immunogenic epitopes.
Finally potential future immunogenicity models are discussed.