Phenotypes associated with this allele

• Allele Symbol: Map6^tm1Job
• Allele Name: targeted mutation 1, Didier Job
• Allele ID: MGI:2388040
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Map6^tm1Job/Map6^tm1Job	either: 129S2/SvPas or (involves: 129S2/SvPas * BALB/c)	MGI:3041140
hm2	Map6^tm1Job/Map6^tm1Job	involves: 129S2/SvPas * C57BL/6	MGI:5694660
ht3	Map6^tm1Job/Map6^+	involves: 129S2/SvPas * C57BL/6	MGI:5694657

Genotype
MGI:3041140

hm1

• Allelic Composition: Map6^tm1Job/Map6^tm1Job
• Genetic Background: either: 129S2/SvPas or (involves: 129S2/SvPas * BALB/c)

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:79099 )

• progeny from heterozygous males and females were viable and displayed no gross anatomical defects

• however, pups born from heterozygous males crossed with homozygous null females died within 24-48 h after birth, regardless of their genotype

behavior/neurological

decreased aggression ( J:79099 )

• in the resident-intruder test, homozygous null mice displayed reduced intermale aggression

increased anxiety-related response ( J:79099 )

• homozygous null mice exhibited significantly increased anxiety-like behavior in the light/dark test, spending virtually all of their time in the dark compartment with very few transitions between the light and dark compartments

akinesia ( J:79099 )

• these same mice also went through periods of freezing behavior, during which they remained still and unreactive to the environment

hyperactivity ( J:79099 )

• homozygous null mice exhibited phases of intense activity, without goal orientation, accompanied by an increased number of activity shifts, with a high occurrence of phases of walk and stillness

circling ( J:79099 )

• occasionally, mutant mice displayed crisis, lasting over 20 minutes, and continuously circled the cage or displayed a burrowing motion

abnormal sleep pattern ( J:79099 )

• relative to wild-type, homozygous null mice spent more time walking or remaining immobile while awake, with a decrease in the time spent feeding and sleeping

• in wild-type mice, 71% of the sleeping phases were preceded by a phase of grooming; the corresponding frequency was 47% in homozygous null mice, when the expected value for random activities was 35%

abnormal pup retrieval ( J:79099 )

♀ • homozygous null females emitted the olfactory cues necessary for suckling and displayed normal lactation

♀ • however, mutant females, although never aggressive towards their pups, showed impaired pup retrieval

♀ • defects in nurturing behavior did not improve with multiple pregnancies and were independent of organic defects or hormonal status

social withdrawal ( J:79099 )

• in the resident-intruder test, homozygous null mice displayed dramatically decreased active social investigation

nervous system

nervous system phenotype ( J:79099 )

N • homozygous null mice showed normal brain organization and histology

N • mutants exhibited no evidence of neuronal degeneration or abnormalities in cellular layering, sensory patterning, or axonal and dendritic organization, despite a significant loss of microtubule cold stability in both neuronal and non-neuronal (e.g. glial, fibroblast) microtubules

N • homozygous null mice exhibited normal olfactory bulb patterning, and normal barrel field organization in the somatosensory cortex

abnormal synaptic vesicle number ( J:79099 )

• depletion of synaptic vesicle pool

impaired synaptic plasticity ( J:79099 )

• homozygous null mice displayed synaptic abnormalities including depletion of synaptic vesicle pools and defects in both short- and long-term plasticity

• synaptic defects were associated with schizophreniform behavioral deficits that were specifically ameliorated by long-term administration of neuroleptics

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:79099

Genotype
MGI:5694660

hm2

• Allelic Composition: Map6^tm1Job/Map6^tm1Job
• Genetic Background: involves: 129S2/SvPas * C57BL/6

behavior/neurological

abnormal behavioral response to amphetamine ( J:225083 )

• mice injected with the indirect dopamine agonist amphetamine exhibit a greater hyperactivity compared to similarly treated wild-type mice

• maternally deprived mutants show greater hyperactivity after injection of amphetamine than wild-type mice

increased exploration in new environment ( J:225083 )

• mice exhibit enhanced locomotor activity in an open field in a novel environment condition and after saline injection

• mice are hyperactive in response to a novel environment when assessed in a Y-maze test

• maternally deprived mutants are hyperactive in a novel environment condition both in an open field and in a Y-maze test, and after injection of amphetamine

hyperactivity ( J:225083 )

• mice exhibit enhanced locomotor activity in an open field in a novel environment condition and after saline injection

• mice are hyperactive in response to a novel environment when assessed in a Y-maze test

• maternally deprived mutants are hyperactive in a novel environment condition both in an open field and in a Y-maze test, and after injection of amphetamine

• however, spatial working memory in the spontaneous alternation aspect of the Y-maze is normal

induced hyperactivity ( J:225083 )

• mice injected with the indirect dopamine agonist amphetamine exhibit hyperactivity

social withdrawal ( J:225083 )

• mice exhibit deficits in conspecific recognition as they do not exhibit different durations of sniffing over the first 3 trials of an intruder mouse and no recovery at the 4th trial after the introduction of a second intruder mouse as is seen in wild-type mice

nervous system

decreased prepulse inhibition ( J:225083 )

• mice show impaired prepulse inhibition of acoustic startle response using 24 dB prepulses

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:225083

Genotype
MGI:5694657

ht3

• Allelic Composition: Map6^tm1Job/Map6⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

behavior/neurological

increased exploration in new environment ( J:225083 )

• mice are hyperactive in response to a novel environment when assessed in a Y-maze test, indicating short-lasting locomotor hyperactivity in response to acute mild stress

• maternally deprived mutants are hyperactive in a novel environment condition in a Y-maze test and show intermediate activity between that of wild-type and homozygotes in response to novelty in the open field or to amphetamine

hyperactivity ( J:225083 )

• mice are hyperactive in response to a novel environment when assessed in a Y-maze test, indicating short-lasting locomotor hyperactivity in response to acute mild stress

• maternally deprived mutants are hyperactive in a novel environment condition in a Y-maze test and show intermediate activity between that of wild-type and homozygotes in response to novelty in the open field or to amphetamine

• however, locomotor activity in an open field in a novel environment condition and after saline injection is normal, mice injected with amphetamine exhibit a similar locomotor reaction as wild-type mice, and spatial working memory in the spontaneous alternation aspect of the Y-maze is normal

social withdrawal ( J:225083 )

• mice exhibit deficits in conspecific recognition as they do not exhibit different durations of sniffing over the first 3 trials of an intruder mouse and no recovery at the 4th trial after the introduction of a second intruder mouse as is seen in wild-type mice

nervous system

decreased prepulse inhibition ( J:225083 )

• prepulse inhibition of acoustic startle response is slightly impaired, with an intermediate level of response between wild-type and homozygous mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:225083