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Phenotypes Associated with This Genotype
Genotype
MGI:5661462
Allelic
Composition
Ap1s2tm1Pschu/Ap1s2tm1Pschu
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ap1s2tm1Pschu mutation (0 available); any Ap1s2 mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• in a hidden platform Morris water maze assay, mice spend less time in the target quadrant during the acquisition trials, and consistently use longer swimming paths to reach the hidden platform
• however, behavior during training is similar to that in wild-type controls
• at 4 months of age, mice show difficulty in locating the water source when moved between different types of cages
• although grip strength is normal, mice are unable to learn to balance and spend less time on an accelerating rotarod
• however, no ataxia is observed, as swimming velocity and endurance in the water maze are normal
• at 4 months of age, mice display reduced cage activity as determined by the number of light beam crossings within a 24-hr period
• however, neither ambulatory nor qualitative exploratory measures are altered in the open field test

nervous system
• although stimulation with 900 AP/10 Hz increases the number of SVs with diameters >60nm in both groups, mutant resting synapses contain larger organelles more often than wild-type
• at rest, SVs from mutant hippocampal neurons are enlarged with diameters of ~41nm versus ~38nm in controls, and appear more heterogenous
• electron micrographs of hippocampal boutons revealed that mutant resting synapses contain only ~135 SVs per um2 versus ~230 SVs per um2 in wild-type synapses
• after depletion of the SV pool via stimulation with 900 AP/10 Hz, mutant SV numbers are reduced to only ~47 SVs per um2 versus ~105 SVs in wild-type synapses
• at rest, SV numbers of visibly docked SVs per 100-nm active zone are already reduced by 40% in mutant synapses relative to controls
• upon stimulation (900 AP/10 Hz), SV numbers of visibly docked SVs per 100-nm active zone are reduced by 60% in mutant synapses versus only 28% in controls
• in mutant synapses, SVs numbers within a distance of 20 nm to the active zone are reduced to degrees similar to those of docked SVs after stimulation
• mice display impaired recycling and acidification of synaptic vesicles in neonatal hippocampal boutons
• SV recycling analysis using synaptopHluorin (an exo- and endocytosis probe) revealed that weak stimulation of SV exocytosis by 100 APs at 20 Hz resulted in a slight delay in the acidification of endocytosed structures; this is increased by stimulations by 300 Aps at 10 Hz
• after complete depletion of the total recycling SV pool, only 46.5% of exocytosed vesicles become re-available for release relative to 94% in wild-type controls
• in addition, SV reformation is incomplete reaching only 70% of that in wild-type hippocampal neurons

adipose tissue
• adult mice show loss of interscapular and other subcutaneous adipose tissues
• CT scan revealed a ~19 reduction in total adipose tissue volume
• within the body, degree of reduction varies between the different types of adipose tissue
• mice exhibit altered sorting of sortilin in adipocytes leading to inhibition of adipogenesis and lipodystrophy
• ex vivo, primary MEFs isolated from E12.0 mutant embryos show a 65% reduction in adipogenic differentiation relative to wild-type MEFs, as revealed by Red O lipid staining
• vascular stromal stem cells isolated from mutant epididymal adipose tissue show significantly impaired adipogenic differentiation relative to wild-type cells (3.6% vs 6%)
• some mice show complete loss of interscapular adipose tissue, resulting in a hump-like appearance
• at 5 months of age, mice exhibit severe lipodystrophy of subcutaneous adipose tissues

growth/size/body
• at 5 months of age, mice are 15% lighter than wild-type controls
• however, no differences in body weight are noted between 4 and 14 weeks of age, irrespective of diet

cellular
• ex vivo, primary MEFs isolated from E12.0 mutant embryos show a 65% reduction in adipogenic differentiation relative to wild-type MEFs, as revealed by Red O lipid staining
• vascular stromal stem cells isolated from mutant epididymal adipose tissue show significantly impaired adipogenic differentiation relative to wild-type cells (3.6% vs 6%)

integument
• adult mice show loss of interscapular and other subcutaneous adipose tissues

homeostasis/metabolism
N
• mice show no differences in glucose serum homeostasis in a glucose-tolerance assay relative to wild-type controls
• serum levels of IGF-1 and of adipokines (adiponectin, leptin, resisting) are normal
• respiratory coefficient is unaffected

endocrine/exocrine glands
N
• mammary gland development is relatively unaffected as shown by milk duct histology at 4 weeks of age

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
syndromic X-linked intellectual disability 5 DOID:0060800 OMIM:304340
J:218588


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
05/10/2022
MGI 6.19
The Jackson Laboratory