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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 Grin1Rgsc174/Grin1+ Grin1Rgsc174/Grin1Rgsc174 Grin1tm1.1Ese/Grin1tm1.1Ese Grin1tm1.1Phs/Grin1+ Grin1tm1.1Phs/Grin1tm1.1Phs Grin1tm1.1Slab/Grin1+ Grin1tm1Blt/Grin1+ Grin1tm2Blt/Grin1tm2Blt Grin1tm1Bhk/Grin1tm1Bhk
  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