ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

Umemori, Juzoh; Takao, Keizo; Koshimizu, Hisatsugu; Hattori, Satoko; Furuse, Tamio; Wakana, Shigeharu; Miyakawa, Tsuyoshi

doi:10.1186/1756-0500-6-203

Table 3 Mutations in Grin1 cause distinctive behavioral abnormalities

From: ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

		Grin1 ^Rgsc174		Grin1 ^tm1.1Ese	Grin1 ^tm1.1Phs		Grin1 ^tm1.1Slab	Grin1 ^tm1Blt	Grin1 ^tm2Blt	Grin1 ^tm1Bhk
	Mutation	R844C		S897A	N598Q		N598R	D481N	K483Q	Insertion of a neomycin cassette (hypomorphic)
	Site/Domain	C0 domain (interacting with CaMKII, calmodulin, and alpha-actinin)		Phosphorylation site for PKA	Critical channel site		Critical channel site	Glycine binding site	Glycine binding site	Intron 20
	Genotype	Grin1^Rgsc174/Grin1⁺	Grin1^Rgsc174/Grin1^Rgsc174	Grin1^tm1.1Ese/Grin1^tm1.1Ese	Grin1^tm1.1Phs/Grin1⁺	Grin1^tm1.1Phs/Grin1^tm1.1Phs	Grin1^tm1.1Slab/Grin1⁺	Grin1^tm1Blt/Grin1⁺	Grin1^tm2Blt/Grin1^tm2Blt	Grin1^tm1Bhk/Grin1^tm1Bhk
	Effects on receptor function	ND	Increased Ca²⁺ influx [32]	No phosphorylation at S897[29]	No obvious defects [64]	Reduced Ca²⁺ permeability; Altered voltage-dependent Mg²⁺ block [64]	Reduced Ca²⁺ permeability; Lower mean current amplitude mediated by NMDA receptor; Strong reduction of the Mg²⁺ block [65]	5-fold reduction in receptor glycine affinity; Normal glutamate affinity [31]	86-fold reduction in receptor glycine affinity; Normal glutamate affinity [31]	ND
	Cellular/tissue-level effects	Enhanced c-Fos immunoreactivity in the prelimbic cortex [32]	ND	Abnormal glutamate mediated receptor currents; Reduced AMPA-mediated synaptic currents, reduced long-term potentiation [29]	Normal CA3/CA1 synapse LTP [64]	ND	Normal whisker barrel formation in the primary somatosensory cortex [65]	Decreased susceptibility to pharmacologically induced seizures; Reduced LTP [31]	Reduction in glycine concentration-dependent Ca²⁺ influx	ND
	Effects on expression level	Normal [32]	ND	Decreased at synapse [29]	Normal	Normal	Normal	Large increase in Cerebellum; Grin2B shows large increase in Cortex, Striatum, and Cerebrum [31]	ND	Reduced expression to ~10% of normal levels [22]
	Physical phenotype	Decreased body weight [present study, 32]	Premature death (Embryonic 17th day to 4 weeks) [32]	ND	Premature death [64]	Death ~1 hr after birth; respiratory distress; no feeding [64]	Perinatal death ~6 hr from birth [65]	Normal development [31]	Postnatal lethality, decreased body weight	Decreased body weight [22]; Reduced male fertility [22]
	Locomotor activity	Increased in OF and HC [present study, 32]	ND	Normal in HC [29]	Increased before delivery (Pregnant females) [64]	ND	Increased (Newborn) [65]	ND	ND	Increased during habituation in OF [22, 23]; Normal in HC [23]
	Social behavior	Shorter interaction with other subject in OF [32]; Increased social novelty preference in CSI [present study]	ND	Abnormal social investigation [29]	ND	ND	ND	Social approach deficit [30]	ND	Social withdrawal, escape behaviors, reduced social investigation in RI [22]; Lower approach toward the stimulus mouse in TCS [23]; No preference for unfamiliar mouse in SA [24];
Behavioral phenotypes	Anxiety-like behavior	Decreased transition in LD; Increased time spent in open arm in EP [present study]	ND	ND	ND	ND	ND	Increased spent time in open arm of EP [30]; Increased time spent in center of OF [31]; Increased time exploring object [30]; No difference in LD [31];	ND	Increased time spent in open arm in EZ [23]; Increased time spent in the central zone in OF [23]
	Startle response	Decreased [present study]	ND	Normal [29]	ND	ND	ND	Increased [31]	ND	Increased [24]
	Prepulse inhibition	No significant difference between genotypes	ND	Decreased [29]	ND	ND	ND	Normal	ND	Decreased [24]; Increased amplitudes for auditory and visual ERPs [23]
	Working memory	No obvious deficit	ND	ND	ND	ND	ND	Abnormal spatial learning in MWM [31]	ND	ND
	Fear memory	Decreased	ND	ND	ND	ND	ND	ND	ND	ND
	Other behavioral phenotypes	Increased exploration [32]; Normal depression-like behavior in TS and PS [present study]	ND	ND	Abnormal nest building; Abnormal maternal nurturing (abnormal maternal grooming, abnormal pup retrieval, pup cannibalization) [64]	ND	ND	Impaired motor coordination in horizontal wire test [31]	No suckling reflex	Potential impairments in olfaction [76]; Reduced nest building behavior [23]
	Background	C57BL/6J	C57BL/6J	C57BL/6	129S1/Sv × 129X1/SvJ × C57BL/6		129P2/OlaHsd × C57BL/6J	129P2/OlaHsd × C57BL/6	129P2/OlaHsd × C57BL/6	129P2/OlaHsd × C57BL/6 × DBA/2

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ISSN: 1756-0500

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