Phenotypes associated with this allele

• Allele Symbol: Cox10^tm1Ctm
• Allele Name: targeted mutation 1, Carlos T Moraes
• Allele ID: MGI:3605782
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cox10^tm1Ctm/Cox10^tm1Ctm Slc6a3^tm1.1(cre)Bkmn/?	B6.Cg-Cox10^tm1Ctm Slc6a3^tm1.1(cre)Bkmn	MGI:5775427
cn2	Cox10^tm1Ctm/Cox10^tm1Ctm Myl1^tm1(cre)Sjb/Myl1^+	involves: 129X1/SvJ * C57BL/6	MGI:3609951
cn3	Cox10^tm1Ctm/Cox10^tm1Ctm Tg(Camk2a-cre)#Szi/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * CBA	MGI:5444474

Genotype
MGI:5775427

cn1

• Allelic Composition: Cox10^tm1Ctm/Cox10^tm1Ctm; Slc6a3^{tm1.1(cre)Bkmn}/?
• Genetic Background: B6.Cg-Cox10^tm1Ctm Slc6a3^{tm1.1(cre)Bkmn}

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:231810 )

• mice exhibit a decline in motor activity and coordination by 2 months of age, maximum decline is reached by 4 months of age

impaired coordination ( J:231810 )

• mice are not able to perform the pole test by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance

• impaired rotarod performance by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance

• walking time is decreased on rotarod at 4 and 6 months as compared to younger animals

decreased vertical activity ( J:231810 )

• decrease in rearing activity by 2 months of age, maximum decline is reached by 4 months of age

decreased locomotor activity ( J:231810 )

• mice move less during nocturnal cycle and in open field test (distance travelled) as compared to controls; treatment with high dose L-DOPA (25 mg/kg) results in hyperactivity and stereotypic movements

• maximum decline in motor performance is reached at 4 months of age

hematopoietic system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

growth/size/body

decreased body weight ( J:231810 )

• pups are born at a lower body weight than controls and remain at a lower weight throughout life

• administration of pioglitazone increases weight to control levels

immune system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

abnormal chemokine secretion ( J:231810 )

• CXCL10 and CCL2 are increased in striatum

• in midbrain, levels of IL6, IL10, CXCL10 and CCL2 trend upward, but do not reach significance

increased interleukin-1 beta secretion ( J:231810 )

• increase in IL1B in midbrain in 2 month old mice

• IL1B is slightly increased in striatum but does not reach significance

homeostasis/metabolism

decreased dopamine level ( J:231810 )

• decrease in dopamine and dopamine metabolites (to a lesser extent) in striatum by 2 months of age as compared to controls

• dopamine depletion continues through out life but does not worsen

nervous system

microgliosis ( J:231810 )

increased microglial cell activation ( J:231810 )

• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity

• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

decreased dopaminergic neuron number ( J:231810 )

loss of dopaminergic neurons ( J:231810 )

• substantial loss of dopaminergic cell bodies in the substantial nigra as measured by reduction of tyrosine hydroxylase (TH) and dopamine transporter (DAT) content

• widespread axonal degeneration in striatum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:231810

Genotype
MGI:3609951

cn2

• Allelic Composition: Cox10^tm1Ctm/Cox10^tm1Ctm; Myl1^tm1(cre)Sjb/Myl1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:101747 )

• mutant mice have a shorter life span

• females died younger than males

muscle

abnormal skeletal muscle morphology ( J:101747 )

• showed areas of mitochondrial proliferation and markedly enlarged and swollen mitochondria

• no signs of fibrosis, inflammation, or apoptosis were seen

increased variability of skeletal muscle fiber size ( J:101747 )

• mutant muscle fibers are more heterogeneous in size

decreased skeletal muscle mass ( J:101747 )

• at 3-4 months of age, severe reductions in muscle mass are seen

increased muscle fatigability ( J:101747 )

• maximal force evoked in mutant muscle is significantly smaller

• the muscles from mutant mice are more fatigable than control

myopathy ( J:101747 )

• 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/body

weight loss ( J:101747 )

• at 3-4 months of age, they started to lose weight

• female mutant mice weigh less at an early age

skeleton

kyphosis ( J:101747 )

• starting at 3-4 months of age

behavior/neurological

decreased locomotor activity ( J:101747 )

• 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		DO ID	OMIM ID(s)	Ref(s)
mitochondrial myopathy		DOID:699	OMIM:251900	J:101747

Genotype
MGI:5444474

cn3

• Allelic Composition: Cox10^tm1Ctm/Cox10^tm1Ctm; Tg(Camk2a-cre)#Szi/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6J * CBA

mortality/aging

premature death ( J:188773 )

• die between 8 and 12 months of age

growth/size/body

decreased body weight ( J:188773 )

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

behavior/neurological

impaired coordination ( J:188773 )

• decrease in rotarod performance first seen at 3 and 4 months of age for males and females, respectively

abnormal locomotor activation ( J:188773 )

• 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

abnormal mitochondrial physiology ( J:188773 )

• 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

decreased brain weight ( J:188773 )

• brain weight is normal at 1-4 months of age, however by 8 months of age, brains weigh about half of control weight

abnormal cerebral cortex morphology ( J:188773 )

• severe cortical atrophy by 8 months of age

abnormal cingulate gyrus morphology ( J:188773 )

• neuronal cell death in the cingulate cortex at 4 months of age, but not earlier

abnormal piriform cortex morphology ( J:188773 )

• mutants show oxidative damage in the piriform cortex at 4 months of age and neuronal cell death at this time but not earlier

neurodegeneration ( J:188773 )

• 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

neuron degeneration ( J:188773 )

• mutants consistently show neuronal cell death in the cingulate cortex, piriform cortex, and hippocampus/dentate gyrus at 4 months of age, but not earlier

hippocampal neuron degeneration ( J:188773 )

• the hippocampus/dentate gyrus and CA1 region shows neuronal loss at 4 months of age

abnormal nervous system physiology ( J:188773 )

• mutants show metabolic changes in the brain, with elevated levels of lactate and a decrease in n-acetyl aspartate

abnormal glial cell physiology ( J:188773 )

• 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

abnormal enzyme/coenzyme activity ( J:188773 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cytochrome-c oxidase deficiency disease		DOID:3762	OMIM:PS220110	J:188773