Knockout and transgenic (overexpression) studies with mice: (patho)physiologic functions of mAC isoforms
Because of the lack of selective mAC inhibitors and antibodies, advances in our knowledge on the functions of mACs isoforms largely depended on knockout and overexpression studies in mice. Table updated from Sadana and Dessauer (2009). With few exceptions, the table does not consider associations of ADCY gene polymorphisms with diseases in humans.
| AC Isoform | Availability of | (Patho)physiologic Functions (Mice and Humans) | |
|---|---|---|---|
| Knockout (mice) | Overexpression (mice) | ||
| AC1 | Yes | Yesa | Mice: Learning, memory, synaptic plasticity, opiate withdrawal and cocaine sensitization, behavioral inhibition, brain development, pain |
| AC2 | No | No | Mice: No data available |
| Humans: AC2 impairment in Lesch-Nyhan syndrome (Kinast et al., 2012)? | |||
| AC3 | Yes | No | Mice: Olfactory and pheromone responses, olfactory dependent and contextual memory, sperm function, diet-induced obesity, maternal behavior, inter-male aggressiveness |
| AC4 | Yesb | Mice: No phenotype | |
| AC5 | Yes | Yesa | Mice: Cardiac contraction, motor coordination, striatum-dependent learning, opiate and ethanol dependency, pain responses, diet-induced obesity, renin secretion, stress responses. |
| Humans: AC5 gain of function in human movement disorders associated with dystonia, myokymia and chorea (Chen et al., 2012c, 2014b) | |||
| AC6 | Yes | Yesa | Mice: cardiac contraction and calcium sensitivity, polycystic kidney disease and renal function including mild Bartter syndrome, sympathetic tone, bone adaptations, pancreatic fluid secretion |
| AC7 | Yes | Yesa | Mice: Ethanol dependency, depression, immune function |
| AC8 | Yes | Yesa | Mice: Learning, memory, synaptic plasticity, opiate withdrawal, mood disorders, anxiety behavior, glucose homeostasis |
| AC9 | Yesc | No | Mice: Immune response in monocytes, possible links to sepsis and cardiac repolarization |
↵a Cardiac or brain directed overexpression.
↵b Tissue-specific expression in kidney collecting duct (Kittikulsuth et al., 2014a).
↵c Unpublished results and International Mouse Phenotyping Consortium (http://www.mousephenotype.org/).