Leadership In Controlled Gene Expression

Tet Mouse Models for Biomedical Research

Conventional transgenic and knockout mice are not only widely used in basic research, but are also important tools to  model human diseases as they allow researchers to study gene function in the context of a whole mammalian organism. However, these studies have certain limitations as the knockout or overexpression of a gene during embryonic development may result in embryonic or perinatal lethality, thus preventing studies of the effects of particular gene ablations in adult animals. Furthermore as conventional gene deletions are irreversible they do not permit analysis of gene functions at a particular developmental stage. Finally, unwanted physiological or toxic effects may result from unregulated overexpression of transgenic gene products.

As proven by numerous Tet transgenic mouse publications, the Tet Technology can circumvent these technical hurdles and allows control of in vivo gene expression quantitatively, in a time- and tissue-specific and reversible manner.Furthermore the Tet Technology not only turns a target gene on or off, but also supports intermediate levels that mimic pathological states more closely than ‘all-or-none’ switches.

For these reasons Tet transgenic mouse models can address early events during the onset of disease, disease progression, potential reversibility of pathologies and disease regression. Disease models of this quality are highly valuable not only for the identification of genes and their products as pharmacological targets, but also for preclinical drug-efficacy studies. Examples for existing Tet transgenic mouse models of human diseases include (i) autoimmunity in diabetes type I, (ii) lung development, (iii)airway remodelling in asthma, (iv) osteoarthritis, (v) Alzheimers disease  (vi) B-cell leukemia, (vii) Prion diseases, and (viii) Huntington disease. In some of these models, the temporal program of pathological processes and its potential reversibility was examined. Interestingly, many pathological states could be abrogated or even reversed by repressing the disease-causing gene demonstrating the power of the Tet gene switch.