Mouse Genome Informatics
cn1
    Cox10tm1Ctm/Cox10tm1Ctm
Myl1tm1(cre)Sjb/Myl1+

involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant mice have a shorter life span
• females died younger than males

muscle
• showed areas of mitochondrial proliferation and markedly enlarged and swollen mitochondria
• no signs of fibrosis, inflammation, or apoptosis were seen
• mutant muscle fibers are more heterogeneous in size
• at 3-4 months of age, severe reductions in muscle mass are seen
• maximal force evoked in mutant muscle is significantly smaller
• the muscles from mutant mice are more fatigable than control
• mutant mice are healthy until approximately 3 months of age then develop a slowly progressive myopathy
• the myopathy starts earlier and worsens quicker in female

growth/size
• at 3-4 months of age, they started to lose weight
• female mutant mice weigh less at an early age

skeleton
• starting at 3-4 months of age

behavior/neurological
• starting at 3-4 months of age
• in treadmill performance test, 2-month old mutant mice had difficulty in performing the task
• the female performance was significantly poorer than males

Mouse Models of Human Disease
OMIM IDRef(s)
Mitochondrial Myopathy 251900 J:101747


Mouse Genome Informatics
cn2
    Cox10tm1Ctm/Cox10tm1Ctm
Tg(Camk2a-cre)#Szi/0

involves: 129X1/SvJ * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 8 and 12 months of age

growth/size
• mutants weight less than littermate controls after 4 and 5 months of age, for females and males, respectively

behavior/neurological
• decrease in rotarod performance first seen at 3 and 4 months of age for males and females, respectively
• at 3 months of age, mutants start to decrease their nocturnal activity and by 4 months, cycles of hyperactivity are seen and continue throughout their life span

cellular
• mutants exhibit 80% of mitochondrial respiratory complex IV (CIV) activity of control levels in the cortex at 1 month of age and 33% of control levels by 4 months of age
• mutants exhibit decreased CIV activity in the hippocampus as well

nervous system
• brain weight is normal at 1-4 months of age, however by 8 months of age, brains weigh about half of control weight
• severe cortical atrophy by 8 months of age
• neuronal cell death in the cingulate cortex at 4 months of age, but not earlier
• mutants show oxidative damage in the piriform cortex at 4 months of age and neuronal cell death at this time but not earlier
• mutants exhibit progressive encephalopathy, with small lesions in the piriform cortex at 4 months of age, lesions in the striatum, outer cortical layers and hippocampus by 6 months of age, and massive degeneration of the cortex by 8 months of age
• mutants consistently show neuronal cell death in the cingulate cortex, piriform cortex, and hippocampus/dentate gyrus at 4 months of age, but not earlier
• the hippocampus/dentate gyrus and CA1 region shows neuronal loss at 4 months of age
• mutants show metabolic changes in the brain, with elevated levels of lactate and a decrease in n-acetyl aspartate
• mutants exhibit a dramatic increase in GFAP immunoreactivity in the cortex and somewhat smaller increase in the hippocampus and piriform cortex at 4-5 months of age, indicating reactive glia

homeostasis/metabolism
• mutants exhibit decreased mitochondrial respiratory complex IV enzymatic activity in the cortex and hippocampus

Mouse Models of Human Disease
OMIM IDRef(s)
Mitochondrial Complex IV Deficiency 220110 J:188773