Phenotypes associated with this allele

• Allele Symbol: Gria1^tm1Rsp
• Allele Name: targeted mutation 1, Rolf Sprengel
• Allele ID: MGI:2178057
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gria1^tm1Rsp/Gria1^tm1Rsp	B6.129-Gria1^tm1Rsp	MGI:3588768
hm2	Gria1^tm1Rsp/Gria1^tm1Rsp	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3805109
hm3	Gria1^tm1Rsp/Gria1^tm1Rsp	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:4888959
hm4	Gria1^tm1Rsp/Gria1^tm1Rsp	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:4888960

Genotype
MGI:3588768

hm1

• Allelic Composition: Gria1^tm1Rsp/Gria1^tm1Rsp
• Genetic Background: B6.129-Gria1^tm1Rsp

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

increased anxiety-related response ( J:167264 )

• in the elevated zero-maze, mutants make fewer open entries

decreased chemical nociceptive threshold ( J:96597 )

• reduction in nociceptive responses in phase II of formalin test and a significantly longer duration of nocifensive behaviors during phase I of formalin test

abnormal nociception after inflammation ( J:96597 )

• increased spontaneous nocifensive responses to intraplantar capsaicin, however exhibit normal spinal nociceptive tail flick reflex in response to noxious heat and hindpaw withdrawal in response to thermal or mechanical stimuli

nervous system

abnormal spinal cord morphology ( J:96597 )

• number of Ca²⁺-permeable AMPA channels is decreased in laminae of the spinal cord

impaired synaptic plasticity ( J:96597 )

• loss of acute, short-term nociceptive plasticity in the spinal dorsal horn

reduced AMPA-mediated synaptic currents ( J:96597 )

• the AMPA/NMDA peak current ratio and current integral ratio are significantly reduced in spinal neurons

• AMPA channel-mediated peak currents on second-order spinal neurons are significantly reduced

Genotype
MGI:3805109

hm2

• Allelic Composition: Gria1^tm1Rsp/Gria1^tm1Rsp
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

decreased body size ( J:55695 )

• mice are smaller than wild-type littermates during first postnatal weeks, but size normalizes post-weaning

nervous system

nervous system phenotype ( J:55695 )

N • pyramidal cells from hippocampal CA1 region have normal dendrites and spines, and normal morphology of excitatory synapses relative to controls

N • dendritic and spontaneous calcium transients are similar in mutants and wild-type mice

reduced AMPA-mediated synaptic currents ( J:55695 )

• AMPA currents measured in membrane patches from acute brain slices are strongly reduced compared to wild-type

reduced long-term potentiation ( J:55695 )

• in CA1 slices from adult mice, tetanization produces a persistent potentiation of synaptic responses indicated by increased average field EPSP slopes in wild-type, but mutant mice show no LTP (fEPSPs are not different from pretetanic controls

• in presence of bicuculline, LTP is absent in mutants but tetanized wild-type controls show 140% (control pathway: 100%) LTP

• paired-pulse facilitation at CA1 excitatory synapses is similar between mutants and controls

behavior/neurological

behavior/neurological phenotype ( J:55695 )

N • no deficits in spatial learning or spatial memory acquisition are observed in mutants compared to controls

abnormal behavioral response to xenobiotic ( J:75498 )

• unlike wild-type, mice do not show significant tolerance to the antinociceptive effect of morphine as determined by the thermal tail flick test; repeated doses with increasing doses of morphine that produce tolerance in wild-type to the antinociceptive effects still produce significant nociception in mutants

• animals display enhanced context-dependent sensitization to D-amphetamine compared to wild-type or Gria1^tm1Erk mice

decreased behavioral withdrawal response ( J:75498 )

• mice show a lower number of naloxone-precipitated behavioral withdrawal symptoms with chronic morphine treatment compared to wild-type littermates

abnormal response to new environment ( J:75498 )

• mice are slightly hyperactive when placed in a novel cage, but do show habituation upon repeated exposure to novel cages

• upon repeated exposure, both mutants and wild-type show habituation but mutants still show slight difference in ambulation

increased exploration in new environment ( J:101930 )

• male mice kept isolated for 1, 5, or 21 days show increased duration of passive exploration of environment compared to wild-type littermates

decreased aggression towards male mice ( J:101930 )

• in resident-intruder test, individually tested male mice isolated for 1, 5, or 21 days show reduced frequency and duration of consummate and ambivalent aggression towards an intruder in the resident animal's cage

• after 30 days in isolation, male mutants do not show increased consummate aggression towards other animals when placed together, in contrast to wild-type males which show high levels of aggression towards other males

• mutants show a greater duration of defensive behavior after 30 days of isolation than wild-type males

• after pair-housing with a female for 5 days, mutants show no increased aggressive behavior toward an intruder male whereas aggression is higher in wild-type males

decreased anxiety-related response ( J:101930 )

• in elevated plus-maze tests, mutant show shorter latencies to enter closed to first entry of open arms, decreased freezing and more entries into open arms compared to wild-type littermates

abnormal locomotor behavior ( J:75498 , J:101930 )

• increased locomotor activity response to morphine injection is greater than wild-type; however baseline values are higher than controls (J:75498)

• duration of locomotor activity is slightly higher than controls in males kept isolated for 1, 5, or 21 days (J:101930)

hyperactivity ( J:75498 )

• slightly hyperactive in novel environment

increased vertical activity ( J:101930 )

• rear frequency and duration are increased compared to controls in male mice isolated for 1, 5, or 21 days

abnormal sexual interaction ( J:101930 )

♂ • males exhibit less sniffing of body of females than wild-type males

abnormal social investigation ( J:101930 )

♂ • frequency and duration of partner exploration are increased in male mice isolated for 1, 5, or 21 days compared to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:75498 , J:101930 )

N • following morphine injection, both mutant and wild-type mice show similar morphine levels in brain tissue and plasma samples, indicating similar pharmacokinetics between the genotypes (J:75498)

N • after 4 weeks of social isolation, dopamine levels in the brain of males are similar to controls, as are plasma testosterone levels (J:101930)

abnormal serotonin level ( J:101930 )

• ratio of 5-hydroxyindoleacetic acid to serotonin in hippocampus are lower than in wild-type after 4 weeks of social isolation; in general, ratios are lower in mutant brains, but only significant decrease is detected in hippocampus

Genotype
MGI:4888959

hm3

• Allelic Composition: Gria1^tm1Rsp/Gria1^tm1Rsp
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

behavior/neurological

abnormal emotion/affect behavior ( J:167264 )

• in the elevated plus-maze, mutants make more open and center entries and have more center time but less closed time, than wild-type mice

• lithium treatment partially rescues the elevated maze test phenotype, with mutants making fewer open entries compared to untreated mutants

• in the light/dark emergence test, mutants make more shelter exits and show more frequent scanning of the shelter than wild-type, although they do not spend more time out of the shelter than wild-type mice, indicating an increase in risk assessment

• in repeated exposure to elevated plus-maze, mutants make more open entries than wild-type, regardless of trial, and exhibit more open time; mutants make more closed arm entries on trial 2 but not trial 1

• all these behaviors are indicative of manic-like phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizoaffective disorder		DOID:5418		J:167264

Genotype
MGI:4888960

hm4

• Allelic Composition: Gria1^tm1Rsp/Gria1^tm1Rsp
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

behavior/neurological

abnormal emotion/affect behavior ( J:167264 )

• in the elevated plus-maze, mutants make more open and center entries and have more center time but less closed time, than wild-type mice

• mutants exhibit a decrease in immobility compared to wild-type during the first and sometimes second forced swim trials

• mutants, but not wild-type mice, exhibit a significant increase in immobility by the third forced swim trial, as compared to trial 1

• mutants show less immobility and increased swimming, but no difference in climbing, in a modified forced swim test compared to wild-type mice on trial 1 but not trial 2

• mutants, but not wild-type mice, exhibit an increase in immobility and a decrease in swimming from trial 1 to 2 of the modified forced swim test

• all these behaviors are indicative of manic-like phenotype

increased exploration in new environment ( J:167264 )

• mutants travel farther than wild-type mice in a novel open field

• however, movement in a home cage-like environment is no different from wild-type

hyperactivity ( J:167264 )

• in a novel open field

induced hyperactivity ( J:167264 )

• injection stress produces a transient increase in activity in mutants compared to a decrease in locomotor activity in wild-type mice

• restraint stress produces a greater increase in locomotor activity in mutants than in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:167264 )

N • corticosterone levels are similar in mutants as in wild-type after a single forced swim trial

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizoaffective disorder		DOID:5418		J:167264