Phenotypes Associated with This Genotype

Genotype
MGI:3526398

• Allelic Composition: Plat^tm1Mlg/Plat^tm1Mlg
• Genetic Background: B6.Cg-Plat^tm1Mlg

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

behavior/neurological

behavior/neurological phenotype ( J:89431 )

N • homozygotes show normal footshock sensitivity thresholds relative to wild-type mice

impaired behavioral response to morphine ( J:88913 )

• homozygotes show no significant differences in the antinociceptive effect of morphine or development of its tolerance relative to wild-type mice

• notably, homozygotes display a significant reduction in morphine-induced hyperlocomotion relative to wild-type

• the defect of morphine-induced hyperlocomotion is reversed by exogenous administration of tPA or plasmin into the nucleus accumbens (Nacc)

abnormal active avoidance behavior ( J:89431 )

• homozygotes display poor active avoidance behavior relative to wild-type mice

impaired conditioned place preference behavior ( J:88913 )

• homozygotes display a significant reduction in morphine-induced conditioned place preference

abnormal contextual conditioning behavior ( J:89431 )

• homozygotes display poor contextual fear conditioning behavior relative to wild-type mice, indicating impaired hippocampal function

abnormal cued conditioning behavior ( J:89431 )

• homozygotes display enhanced cue fear conditioning behavior relative to wild-type mice

abnormal motor learning ( J:84875 )

• relative to wild-type, mutant mice exhibit a 28% reduction in both the rate and extent of learning a complex motor paradigm of irregular peg running, indicating impaired cerebellar motor learning

decreased exploration in new environment ( J:89431 )

• homozygotes display no habitation of object exploration relative to wild-type mice

• homozygotes show no reactivity to spatial change (measured as renewed exploration of displaced objects) relative to wild-type mice

decreased anxiety-related response ( J:81694 , J:94733 )

• after up to 3 weeks of daily restraint, homozygotes exhibit absence of stress-induced anxiety in the elevated-plus maze; in wild-type, acute stress resuls in a decrease in open arm entries, with 21 days of daily restraint leading to some habituation (J:81694)

• in response to a low or middle dose of corticotropin-releasing factor (CRF), homozygotes exhibit reduced anxiety (lower number of open arm entries) in the elevated plus-maze, with an increased number of head dips (increased exploration) relative to wild-type (J:94733)

• in response to a high dose of CRF, homozygotes fail to explore the open arms but display a similar number of closed arms entries relative to wild-type mice, indicating normal locomotor activity (J:94733)

decreased vertical activity ( J:89431 )

• in an empty open field, homozygotes show normal horizontal activity but significantly reduced rearing activity relative to wild-type

homeostasis/metabolism

increased circulating corticosterone level ( J:81694 , J:94733 )

• after a 30-min restraint stress, homozygotes exhibit a 30% increase in corticosterone levels relative to wil-type (J:81694)

• unlike wild-type mice, corticosterone levels in mutant mice do not return to pre-stress levels after a 90-min recovery period (J:81694)

• homozygotes show normal up-regulation of corticosterone in response to CRF but sustain elevation of corticosterone level during recovery (J:94733)

reduced thrombolysis ( J:64220 )

• in a model of pulmonary microembolism, wild-type mice are able to clear 125I-microemboli rapidly with complete lysis by 5 hours; in contrast, mutants remain unable to lyse pulmonary microemboli throughout the 5-hr experimental period

decreased dopamine level ( J:88913 )

• homozygotes exhibit loss of morphine-induced dopamine release in the nucleus accumbens (Nacc)

• the defect of morphine-induced dopamine release is reversed by exogenous administration of tPA or plasmin into the Nacc but not into the ventral tegmental area (VTA)

joint swelling ( J:75303 )

• in a model of collagen-induced arthritis, 60% of mutant mice have 3 or 4 affected limbs compared with only 18% of wild-type mice

• in arthritic mutants, 45% of affected individual limbs display severe swelling and/or rigidity compared with only 19% from wild-type

• there are no differences in the degree of swelling (i.e. paw thickness) between limbs from mutant and wild-type mice with the same clinical score

abnormal acute phase protein level ( J:75303 )

• in a model of collagen-induced arthritis, severely affected joints from homozygotes display diffuse fibrin(ogen) deposition relative to wild-type

• within arthritic joints, higher fibrin levels appear to correlate with increased disease severity

abnormal cytokine level ( J:75303 )

• in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant increase in interleukin-1beta levels in the synovium relative to wild-type

• in a model of collagen-induced arthritis, ankle joint washouts from arthritic homozygotes exhibit a significant increase in TNF levels relative to wild-type

immune system

abnormal acute phase protein level ( J:75303 )

• in a model of collagen-induced arthritis, severely affected joints from homozygotes display diffuse fibrin(ogen) deposition relative to wild-type

• within arthritic joints, higher fibrin levels appear to correlate with increased disease severity

abnormal cytokine level ( J:75303 )

• in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant increase in interleukin-1beta levels in the synovium relative to wild-type

• in a model of collagen-induced arthritis, ankle joint washouts from arthritic homozygotes exhibit a significant increase in TNF levels relative to wild-type

chronic joint inflammation ( J:75303 )

• in a model of collagen-induced arthritis, homozygotes develop significant joint inflammation and joint destruction relative to wild-type mice

• severely affected joints from arthritic homozygotes exhibit massive cell infiltration and higher proteoglycan depletion than wild-type mice

autoimmune arthritis ( J:75303 )

• in a model of collagen-induced arthritis, homozygotes develop a significantly more severe arthritis than wild-type mice

• 95% of mutant mice develop arthritis compared with 68% of wild-type mice; no difference in the day of disease onset is observed

• severely affected joints from arthritic homozygotes exhibit higher cartilage damage and bone erosions than wild-type mice

muscle

muscle phenotype ( J:68083 )

N • in response to glycerol-induced injury, homozygotes exhibit normal skeletal muscle regeneration after 5 days; regeneration is complete after 9 days

N • at 7 days after injury, most injured fibers regenerate into groups of centrally nucleated myotubes, indicating advanced regeneration; only few necrotic fibers are observed

N • at 20 days after injury, virtually no signs of muscle injury are detected, except for centrally located myonuclei inside the regenerated fibers

skeleton

joint swelling ( J:75303 )

• in a model of collagen-induced arthritis, 60% of mutant mice have 3 or 4 affected limbs compared with only 18% of wild-type mice

• in arthritic mutants, 45% of affected individual limbs display severe swelling and/or rigidity compared with only 19% from wild-type

• there are no differences in the degree of swelling (i.e. paw thickness) between limbs from mutant and wild-type mice with the same clinical score

chronic joint inflammation ( J:75303 )

• in a model of collagen-induced arthritis, homozygotes develop significant joint inflammation and joint destruction relative to wild-type mice

• severely affected joints from arthritic homozygotes exhibit massive cell infiltration and higher proteoglycan depletion than wild-type mice

autoimmune arthritis ( J:75303 )

• in a model of collagen-induced arthritis, homozygotes develop a significantly more severe arthritis than wild-type mice

• 95% of mutant mice develop arthritis compared with 68% of wild-type mice; no difference in the day of disease onset is observed

• severely affected joints from arthritic homozygotes exhibit higher cartilage damage and bone erosions than wild-type mice

nervous system

impaired synaptic plasticity ( J:81694 , J:94733 )

• after restraint, homozygotes show reduced neuronal remodeling in the medial amygdala, with absence of stress-induced ERK1/2 phosphorylation at all time points tested (J:81694)

• in response to CRF, homozygotes exhibit attenuated expression of Fos (an indicator of neuronal activation) in the central and medial amygdala but show normal Fos responses in paraventricular nuclei (J:94733)

reduced long-term potentiation ( J:89431 )

• in response to tetanic stimulation, hippocampal CA1 slices from mutant mice show a significant reduction in the late phase of LTP relative to wild-type

• notably, a slight but significant reduction of the early phase of hippocampal LTP is also observed

absent long-term depression ( J:89431 )

• in response to tetanic stimulation of corticostriatal fibers, homozygotes display absence of LTD in a significant portion of striatal neurons