Mouse Genome Informatics
hm
    Map6tm1Job/Map6tm1Job
either: 129S2/SvPas or (involves: 129S2/SvPas * BALB/c)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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
• in the resident-intruder test, homozygous null mice displayed reduced intermale aggression
• 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
• these same mice also went through periods of freezing behavior, during which they remained still and unreactive to the environment
• 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
• occasionally, mutant mice displayed crisis, lasting over 20 minutes, and continuously circled the cage or displayed a burrowing motion
• 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%
• homozygous null females emitted the olfactory cues necessary for suckling and displayed normal lactation (J:79099)
• however, mutant females, although never aggressive towards their pups, showed impaired pup retrieval (J:79099)
• defects in nurturing behavior did not improve with multiple pregnancies and were independent of organic defects or hormonal status (J:79099)
• in the resident-intruder test, homozygous null mice displayed dramatically decreased active social investigation

nervous system
N
• homozygous null mice showed normal brain organization and histology (J:79099)
• 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 (J:79099)
• homozygous null mice exhibited normal olfactory bulb patterning, and normal barrel field organization in the somatosensory cortex (J:79099)
• depletion of synaptic vesicle pool
• 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
OMIM IDRef(s)
Schizophrenia; SCZD 181500 J:79099