Inaktivierung des murinen Gens des Hyperpolarisations-aktivierten Zyklonukleotid-gesteuerten Kationenkanals Typ Drei (HCN3)

The hyperpolarization-activated, cyclic-nucleotide-gated cation
channel (HCN) familiy comprises four members. The channels play a
role in the formation of rhythmic activity of heart and brain. In
contrast to the other three members of the HCN channel family,
there are only a few studies of tissue distribution and
electrophysiological properties of HCN3 so far. Expression has been
reported at low levels, but throughout the brain, in some other
tissues such as retina, olfactory epithelium and recently in the
heart. In order to study the physiological relevance of HCN3
expression, we generated HCN3-deficient mouse lines by gene
targeting and homologous recombination: a complete Knockout, a
complete Knockout expressing the reporter gene lacZ instead of HCN3
and a conditional Knockout using the Cre-loxP system to study
spatial and temporal functions of this pacemaker channel. The
functional characterization included behavioural studies and heart
physiology.