Mouse Genome Informatics
hm1
    Park2tm1Shn/Park2tm1Shn
B6.129S4-Park2tm1Shn/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mitochondria in 12 week old mutant hearts are more disorganized and often found in large clusters with many small, round mitochondria
• following myocardial infarction, mitochondria in myocytes in the border zone are swollen and show severe cristae remodeling
• mitochondria in the heart are smaller but have normal respiratory capacity
• following myocardial infarction, mitophagy is impaired in the border zone of the infarct, but not in remote zones
• myocytes treated with rotenone, a mitochondrial complex I inhibitor, do not show an increase in mitophagy or autophagy as in wild-type myocytes
• isolated myocytes are more susceptible to hypoxia-induced cell death (J:193741)
• in MPP+ treated mouse embryonic fibroblasts (J:194987)
• mitochondria isolated from the border zones and subjected to 4 hours of myocardial infarction, have lower oxygen consumption rates than mitochondria from remote zones

cardiovascular system
• mutants exhibit increased sensitivity to myocardial infarction, with about 60% mortality within the first week compared to about 20% for wild-type mice and show severe thinning of left ventricular wall, enlarged left ventricle interior dimensions, and increased remodeling compared to wild-type
• 7 days following myocardial infarction, surviving mutants exhibit lower fractional shortening and ejection fractions, increased left ventricular end diastolic and systolic dimensions, and increased left ventricular volume, indicating impaired recovery after infarction

growth/size

homeostasis/metabolism
• mutants exhibit increased sensitivity to myocardial infarction, with about 60% mortality within the first week compared to about 20% for wild-type mice and show severe thinning of left ventricular wall, enlarged left ventricle interior dimensions, and increased remodeling compared to wild-type
• 7 days following myocardial infarction, surviving mutants exhibit lower fractional shortening and ejection fractions, increased left ventricular end diastolic and systolic dimensions, and increased left ventricular volume, indicating impaired recovery after infarction

mortality/aging
• mutants exhibit increased sensitivity to myocardial infarction, with about 60% mortality within the first week compared to about 20% for wild-type mice

behavior/neurological
• trained mutant mice remain on rotarod longer than trained wild type at 5, 10, and 15 rpm, but 20 rpm and spend less time "distracted" while on the rod


Mouse Genome Informatics
hm2
    Park2tm1Shn/Park2tm1Shn
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• rotarod performance was normal
• poorer performance in various measures of motor performance

nervous system
• higher than normal levels of dopamine in the striatum
• higher currents are required in striatal neurons to trigger synaptic response

homeostasis/metabolism
• higher than normal levels of dopamine in the striatum

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2 600116 J:86377


Mouse Genome Informatics
cx3
    Gpx1tm1Ysh/Gpx1tm1Ysh
Park2tm1Shn/Park2tm1Shn
Park7tm1Shn/Park7tm1Shn

B6.Cg-Park7tm1Shn Gpx1tm1Ysh Park2tm1Shn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• increased latency to fall (rotarod test) observed at 12 and 18 months of age as compared to controls

homeostasis/metabolism
• striatal dopamine levels are significantly elevated at 6, 12 and 18 months of age, however, dopamine turnover is similar to controls
• striatal serotonin levels are increased at 12 months of age, however, serotonin turnover is similar to controls

nervous system
• striatal dopamine levels are significantly elevated at 6, 12 and 18 months of age, however, dopamine turnover is similar to controls


Mouse Genome Informatics
cx4
    Park2tm1Shn/Park2tm1Shn
Park7tm1Shn/Park7tm1Shn

B6.Cg-Park7tm1Shn Park2tm1Shn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• increased latency to fall (rotarod test) observed at 6, 12, 13, 16 and 18 months of age as compared to controls
• trained mutant mice remain on rotarod longer than trained wild type at all speeds tested (5, 10, 15 and 20 rpm) and spend less time "distracted" while on the rod

homeostasis/metabolism
• striatal serotonin levels are increased at 12 and 18 months of age
• hippocampal serotonin levels are increased in 15 months old mice