TABLE 4.

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

^aCardiac or brain directed overexpression.

^bTissue-specific expression in kidney collecting duct (Kittikulsuth et al., 2014a).

^cUnpublished results and International Mouse Phenotyping Consortium (http://www.mousephenotype.org/).