Phenotypes Associated with This Genotype

Genotype
MGI:5444471

• Allelic Composition: Uqcrfs1^tm1Ctm/Uqcrfs1^tm1Ctm; Tg(Camk2a-cre)#Szi/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * CBA

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

mortality/aging

premature death ( J:188773 )

• sudden death between 3 and 3.5 months of age

growth/size/body

decreased body weight ( J:188773 )

• mutants weight less than littermate controls, especially females

behavior/neurological

impaired coordination ( J:188773 )

• decrease in rotarod performance at 2 months of age, with a rapid decline such that mutants are unable to perform the test 15 days later

decreased locomotor activity ( J:188773 )

• lower nocturnal ambulatory movement than controls

cellular

abnormal mitochondrial physiology ( J:188773 )

• mutants exhibit 43% and 40% of mitochondrial respiratory complex III (CIII) activity of control levels in cortex and hippocampus, respectively, at 1 month of age and 25% and 14% of control levels in cortex and hippocampus, respectively, at 110 days of age

• mutants exhibit an increase in enzymatic activity of mitochondrial respiratory complex IV (CIV) and citrate synthase of 114% and 115%, respectively, at 2.5 months of age in the cortex

• mutants exhibit an increase in enzymatic activity of CIV and citrate synthase to 120% and 121% of control values, respectively, in the hippocampus

increased mitochondrial fission ( J:188773 )

• the ratio of ND1 to actin is higher in mutants at 3 months of age and there is a slight increase in mitochondrial proteins, indicating evidence of mitochondrial proliferation at this time

nervous system

decreased brain weight ( J:188773 )

• at 3 months of age

abnormal somatosensory cortex morphology ( J:188773 )

• neuronal cell death in the somatosensory cortex at 3 months of age right before their death, but not earlier

abnormal piriform cortex morphology ( J:188773 )

• mutants show oxidative damage in the piriform cortex by 1 month of age and neuronal cell death after 3 months of age

neurodegeneration ( J:188773 )

• mutants exhibit progressive encephalopathy, showing lesions in the piriform area at 66 days of age, which worsen and extend to posterior parts of the brain within 18 days

neuron degeneration ( J:188773 )

• mutants consistently show neuronal cell death in the somatosensory cortex, piriform cortex and hippocampus at 3 months of age right before their death, but not earlier

hippocampal neuron degeneration ( J:188773 )

• neuronal cell death in the hippocampus at 3 months of age right before their death, but not earlier

abnormal glial cell physiology ( J:188773 )

• mutants exhibit a slight increase in GFAP immunoreactivity in the cortex, hippocampus, and piriform cortex at 3-3.5 months of age, indicating reactive glia

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:188773 )

• mutants exhibit decreased mitochondrial respiratory complex II enzymatic activity and increased enzymatic activity of mitochondrial respiratory complex IV and citrate synthase in the cortex and hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial metabolism disease		DOID:700		J:188773