Table 1.

Overview of CaMKII mutants and their phenotypes

Mutant^a	Purpose	Molecular characterization^b	Plasticity^b	Behavioral phenotype
αCaMKII-null (−/−)^1,2	Elimination of αCaMKII protein	Expression level of βCaMKII is unaltered^1,2 but targeting of βCaMKII to PSD is increased²	HC-LTP reduced^1-3	Hippocampus-dependent learning severely impaired but learning in some animals is observed after extended training^1,2,6
			NC-LTP reduced in adult animals^4-6
			NC-LTP normal in young animals^4,5
			Decreased PPF¹	Increased seizure susceptibility⁷ (background dependent?²)
			Normal I/O²
αCaMKII-null (+/−)^1,2	Reduction of αCaMKII protein	αCaMKII 50% reduced, βCaMKII levels normal	HC-LTP normal^2,8,9	Normal learning² or reduced hippocampus-dependent learning⁸ (background and protocol dependent)
			NC-LTP reduced⁹
			Decreased PPF⁸
			Increased augmentation⁸	Severely impaired remote memory¹⁰
				Decreased fear and increased aggressive behavior¹¹
αCaMKII-Floxed + CA3-cre¹²	Elimination of αCaMKII protein in CA3 area	αCaMKII is absent from CA3 area after 4 months of age	Increased frequency facilitation	Not tested
			Normal PPF and basal P_r
αCaMKII-T286A¹³	Blocks T286 phosphorylation (no autonomous activity)	Normal expression level of α/βCaMKII; Ca²⁺ -independent activity reduced by 60%	HC-LTP and NC-LTP impaired^13-16	Severely impaired learning in water maze^13,17
			Normal I/O¹³
				Unstable place cells¹⁸
Tg-αCaMKII-T286D¹⁹	Mimics constitutive T286 phosphorylation	Ca²⁺ independent activity two-fold increased	Favors LTD¹⁹	Impaired learning in Barnes maze²¹
			Normal NC-LTP²⁰	Impaired olfactory-based spatial learning²²
			Normal PPF¹⁹	Normal cued and contextual conditioning²¹
				Unstable place cells²³
Tg-αCaMKII-T286D²⁴ (Tet inducible)	Mimics constitutive T286 phosphorylation in an inducible manner	Ca²⁺ -independent activity sixfold increased at maximum induction	Favors LTP at low expression level²⁵	Impaired learning in Barnes maze²⁴
			Favors LTD at high expression level^24,25	Impaired learning in water maze²⁵
			NC-LTP and LTD normal²⁰	Impaired cued and contextual conditioning^24,25
αCaMKII-TT305/6VA²	Blocks T305/T306 (inhibitory) phosphorylation	Increased levels of CaMKII in PSD	Favors LTP	Impaired water maze learning (initial learning okay)
			Normal LTD and I/O
				Impaired reversal learning
				Impaired context discrimination
				Old mice get seizures
αCaMKII-T305D²	Mimics constitutive T305 (inhibitory) phosphorylation	Severely reduced levels of α/βCaMKII in PSD	Favors LTD	Severely impaired in water maze and cued conditioning (cannot learn after over-training)
			No LTP
			Normal LTD and I/O
αCaMKII-Δ3′UTR²⁶	Impairs dendritic targeting of mRNA	Reduced amount of PSD associated CaMKII	Normal (early) LTP	Impaired learning in water maze
			Reduced late-phase LTP	Normal STM but impaired LTM after cued and contextual conditioning
Tg-αCaMKII-F89G²⁷	Inducible system allowing rapid (8 min) reversible decrease of αCaMKII transgene activity	Ca²⁺ -(in)dependent activity twofold to threefold increased without inhibitor	Normal I/O and PPF	Impaired memory consolidation of contextual and cued conditioning when CaMKII activity is changed at the first week after training.
			Enhanced LTD at 3 Hz
			Enhanced LTP at > 10Hz
Ube3A^28,29	Encodes E6-AP ubiquitin ligase; mouse model for Angelman's syndrome	Increased T286-P and T305-P³⁰	Impaired LTP²⁸	Impaired spatial learning^28,29
		Decreased αCaMKII in PSD³⁰	Normal I/O²⁸	Impaired motor coordination^28,29
		Decreased PP1/PP2A activity³⁰		Inducible seizures^28,29

¹Silva et al., 1992; ²Elgersma et al., 2002; ³Hinds et al., 1998; ⁴Glazewski et al., 1996; ⁵Kirkwood et al., 1997; ⁶Gordon et al., 1996; ⁷Butler et al., 1995; ⁸Silva et al., 1996; ⁹Frankland et al., 2001; ¹⁰Frankland et al., 2004; ¹¹Chen et al., 1994; ¹²Hinds et al., 2003; ¹³Giese et al., 1998; ¹⁴Glazewski et al., 2000; ¹⁵Hardingham et al., 2003; ¹⁶Taha et al., 2002; ¹⁷Need et al., 2003; ¹⁸Cho et al., 1998; ¹⁹Mayford et al., 1995; ²⁰Glazewski et al., 2001; ²¹Bach et al., 1995; ²²Wiedenmayer et al., 2000; ²³Rotenberg et al., 1996; ²⁴Mayford et al., 1996; ²⁵Bejar et al., 2002; ²⁶Miller et al., 2002; ²⁷Wang et al., 2003; ²⁸Jiang et al., 1998; ²⁹Miura et al., 2002; ³⁰Weeber et al., 2003.

NC, Neocortex; I/O, input/output (a parameter used to assess synaptic transmission); HC, hippocampus; LTM, long-term memory (24 hr); PSD, postsynaptic density; PPF, paired pulse facilitation; P_r, probability of release; STM, short-term memory (30 min); Tg, transgenic.
↵ a References given in this column refer to primary papers describing the generation and analysis of the mutant. Mutants are made by homologous recombination unless otherwise specified.
↵ b Molecular characterization and plasticity refers to the hippocampus unless otherwise specified.