Phenotypes associated with this allele

• Allele Symbol: Plaur^tm1Mlg
• Allele Name: targeted mutation 1, Richard C Mulligan
• Allele ID: MGI:1934210
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Plaur^tm1Mlg/Plaur^tm1Mlg	B6.Cg-Plaur^tm1Mlg	MGI:3527142
hm2	Plaur^tm1Mlg/Plaur^tm1Mlg	involves: 129S2/SvPas * C57BL/6	MGI:3527128

Genotype
MGI:3527142

hm1

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

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

behavior/neurological

behavior/neurological phenotype ( J:81735 )

N • in the open-field test, homozygotes display normal generalized motor activity relative to wild-type

increased susceptibility to pharmacologically induced seizures ( J:81735 )

• homozygotes exhibit increased susceptibility to pentylenetretrazol (PTZ)-induced seizures, displaying tonic extension and reduced latency time relative to wild-type

decreased exploration in new environment ( J:81735 )

• in the open-field paradigm, wild-type mice occupy the margin of the arena for 66% of the time and the center for 34%, whereas mutants occupy the margin area for 76% of the time and the center for 24%, indicating decreased exploratory behavior

increased anxiety-related response ( J:81735 )

• in the light-dark avoidance test, wild-type mice spend ~50% of the 10 min session exploring the lit side of the chamber whereas mutants occupy the lit side for only 25% of the time, preferring the less aversive, dark area

• in the elevated plus maze, wild-type mice spend ~25-30% of the time in the open arms, whereas mutants spend <5% of the time in the open arms; mutants spend >75% of the time in the closed arms, and ~25% of the time in the center of the maze

myoclonus ( J:81735 )

• ~6% of homozygotes display a novel pattern of spontaneous myoclonic seizures with abnormal bilaterally synchronous interictal discharges during waking behavior; such seizures are occasionally lethal

muscle

myoclonus ( J:81735 )

• ~6% of homozygotes display a novel pattern of spontaneous myoclonic seizures with abnormal bilaterally synchronous interictal discharges during waking behavior; such seizures are occasionally lethal

nervous system

increased susceptibility to pharmacologically induced seizures ( J:81735 )

• homozygotes exhibit increased susceptibility to pentylenetretrazol (PTZ)-induced seizures, displaying tonic extension and reduced latency time relative to wild-type

myoclonus ( J:81735 )

• ~6% of homozygotes display a novel pattern of spontaneous myoclonic seizures with abnormal bilaterally synchronous interictal discharges during waking behavior; such seizures are occasionally lethal

impaired neuronal migration ( J:69135 )

• at at E16.5 and P0, homozygotes display diminished levels of hepatocyte growth factor/scatter factor (HGF/SF), reduced scatter activity in the forebrain, and impaired migration of interneurons from the ganglionic eminence to the cerebral cortex

abnormal brain interneuron morphology ( J:69135 )

• homozygotes display a 50-65% reduction in the number of GABAergic interneurons in frontal and parietal neocortices at E16.5 and P0

abnormal cerebral cortex morphology ( J:69135 )

• in homozygotes, the cortical plate is well-laminated; however, the overall packing density and thickness of the cerebral wall is greater in mutants compared to wild-type

loss of cortex neurons ( J:81735 )

• adult homozygotes show a 50% deficit in GABA+ cells in both anterior cingulate and parietal cortical regions, with almost complete loss of the parvalbumin subtype

• notably, interneuron numbers in piriform and visual cortical areas remain unaffected

loss of GABAergic neurons ( J:81735 )

• adult homozygotes exhibit a significant reduction of GABAergic neurons in the parietal cortex, with regional variation in the reduction of GABA+ cells between frontal and visual cortices

cellular

impaired neuronal migration ( J:69135 )

• at at E16.5 and P0, homozygotes display diminished levels of hepatocyte growth factor/scatter factor (HGF/SF), reduced scatter activity in the forebrain, and impaired migration of interneurons from the ganglionic eminence to the cerebral cortex

Genotype
MGI:3527128

hm2

• Allelic Composition: Plaur^tm1Mlg/Plaur^tm1Mlg
• Genetic Background: involves: 129S2/SvPas * C57BL/6

growth/size/body

growth/size/body region phenotype ( J:31253 )

N • at the age of 4.5 weeks, homozygotes are viable, fertile and display normal growth and histology relative to wild-type mice

hematopoietic system

hematopoietic system phenotype ( J:31253 )

N • relative to wild-type, homozygotes exhibit normal spontaneous lysis of 125I-fibrin-labeled pulmonary plasma clots injected via the jugular vein and embolized to the lungs

abnormal neutrophil physiology ( J:75573 , J:91980 )

• 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit reduced neutrophil influx in the bronchoalveolar lavage fluid relative to wild-type mice (J:75573)

• S. pneumoniae-infected lungs display patchy and dense inflammatory infiltrates composed of monocytes and lymphocytes with relatively few granulocytes (J:75573)

• relative to wild-type, purified neutrophils from mutant mice exhibit a ~50% reduction in superoxide production in response to fMLP (a potent chemotaxin and activator of neutrophils) across the entire dose range tested (J:91980)

• in response to fMLP, mutant neutrophils exhibit normal neutrophil exocytosis of azurophilic granules relative to wild-type neutrophils (J:91980)

• also, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (J:91980)

impaired neutrophil phagocytosis ( J:91980 )

• in vitro, purified neutrophils from mutant mice exhibit a significant reduction in phagocytosis of E. coli at all time points tested

abnormal macrophage physiology ( J:31253 )

• after intraperitoneal injection of thioglycollate, homozygotes show normal invasion of macrophages into the peritoneal cavity

• in vitro, mutant macrophages degrade extracellular matrix proteins at a similar rate as wild-type mice; however, thioglycollate-stimulated peritoneal macrophages from mutant mice show a 3-fold reduction in the initial rate of u-PA-mediated plasminogen activation

immune system

abnormal neutrophil physiology ( J:75573 , J:91980 )

• 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit reduced neutrophil influx in the bronchoalveolar lavage fluid relative to wild-type mice (J:75573)

• S. pneumoniae-infected lungs display patchy and dense inflammatory infiltrates composed of monocytes and lymphocytes with relatively few granulocytes (J:75573)

• relative to wild-type, purified neutrophils from mutant mice exhibit a ~50% reduction in superoxide production in response to fMLP (a potent chemotaxin and activator of neutrophils) across the entire dose range tested (J:91980)

• in response to fMLP, mutant neutrophils exhibit normal neutrophil exocytosis of azurophilic granules relative to wild-type neutrophils (J:91980)

• also, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (J:91980)

impaired neutrophil phagocytosis ( J:91980 )

• in vitro, purified neutrophils from mutant mice exhibit a significant reduction in phagocytosis of E. coli at all time points tested

abnormal macrophage physiology ( J:31253 )

• after intraperitoneal injection of thioglycollate, homozygotes show normal invasion of macrophages into the peritoneal cavity

• in vitro, mutant macrophages degrade extracellular matrix proteins at a similar rate as wild-type mice; however, thioglycollate-stimulated peritoneal macrophages from mutant mice show a 3-fold reduction in the initial rate of u-PA-mediated plasminogen activation

abnormal cytokine level ( J:75573 )

• surprisingly, 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit higher levels of cytokines and chemokines (IL-1beta, IL-6, KC, and CXCL2) in lung homogenates relative to wild-type

increased susceptibility to bacterial infection ( J:75573 )

• 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit an attenuated antibacterial host defense, with more pneumococci (CFU) in their lungs

• as a result, mutants succumb to pneumococcal pneumonia much earlier than wild-type mice

cardiovascular system

cardiovascular system phenotype ( J:82604 )

N • in response to laser-induced injury of the Bruch's membrane, homozygotes display robust choroidal neovascularization at the site of trauma similiar that observed in wild-type mice

homeostasis/metabolism

abnormal cytokine level ( J:75573 )

• surprisingly, 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit higher levels of cytokines and chemokines (IL-1beta, IL-6, KC, and CXCL2) in lung homogenates relative to wild-type

cellular

impaired neutrophil phagocytosis ( J:91980 )

• in vitro, purified neutrophils from mutant mice exhibit a significant reduction in phagocytosis of E. coli at all time points tested