Phenotypes Associated with This Genotype

Genotype
MGI:5469320

• Allelic Composition: mt-Nd6^m3Dwa
• Genetic Background: B6.129S-mt-Nd6^m3Dwa

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

Swelling and loss of retinal ganglion cell axons in mt-Nd6^m3Dwa mice

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:301716 )

• mice exposed to a graded pharmacologic challenge with increasing exposure to flurothyl ether, a GABA-receptor antagonist, begin seizing at a lower concentration of flurothyl ether than wild-type mice, indicating mice are more susceptible to induced seizures

• however, EEG recordings do not show spontaneous seizure activity

increased anxiety-related response ( J:301716 )

• mice show an increase in time spent freezing and the number of times that they exhibit freezing behavior when placed in the center of the open field chamber, indicating increased anxiety when exposed to a threatening environment

• however, in the open field, no difference is seen in the time spend in the center of the open field chamber and mice do not exhibit a gross motor deficit

• in the elevated zero maze, mice spend less head time in the open arm than controls, indicating increased anxiety, without any difference in the number of times mice approach the open arm

increased freezing behavior ( J:301716 )

• in the fear conditioning test, mice remember the earlier shock similarly to wild-type mice, however mice respond more strongly by exhibiting increased freezing behavior

decreased social novelty preference ( J:301716 )

• mice spend less time sniffing the novel mouse than wild-type mice

increased stereotypic behavior ( J:301716 )

• mice bury more marbles than wild-type mice in the marble burying test, indicating increased compulsive behavior

decreased social investigation ( J:301716 )

• in the three-chamber social interaction test, mice at 2 months of age, do not differentiate between social and non-social chambers unlike wild-type mice which spend more time in the social chamber

cellular

abnormal mitochondrial morphology ( J:192260 )

• mitochondria in retinal ganglion cell axons are hollowed and possess irregular cristae

abnormal cellular respiration ( J:192260 )

• reduced liver mitochondria complex I activity with reduced oxygen consumption

abnormal mitochondrial physiology ( J:192260 , J:301716 )

• reduced liver mitochondria complex I activity with reduced oxygen consumption (J:192260)

• synaptosomes.exhibit reduced complex I activity and increased forward but not reverse reactive oxygen species production (J:192260)

• the cortex shows a global reduction in mitochondrial respiration, this includes a decrease in basal respiration (routine), complex I-linked respiration (substrates pyruvate, malate, and glutamate), adenosine diphosphate (ADP)-stimulated respiration, and complex II-linked (Suc) respiration (J:301716)

• the hippocampus shows a difference in the carbonyl cyanide-4-(trifluoromethoxy) phenylhydrzone (FCCP)-stimulated maximum respiration (J:301716)

• mitochondrial ROS production is increased in the cortex in association with complex I and complex II respiration with ADP as well as for FCCP-stimulated maximum respiration (J:301716)

• however, no difference in mitochondrial respiration is seen in the olfactory bulb and mitochondrial ROS production is not increased in any of the respiration states of the hippocampus or olfactory bulb (J:301716)

abnormal respiratory electron transport chain ( J:192260 )

• liver mitochondria exhibit increased forward electron flow but lack of reverse electron flow reaction oxygen species production

• synaptosomes exhibit reduced complex I activity and increased forward but not reverse reactive oxygen species production

increased mitochondrial fission ( J:192260 )

• in retinal ganglion cell axons

oxidative stress ( J:301716 )

• mitochondrial ROS production is increased in the cortex

• however, mitochondrial ROS production is not increased in any of the respiration states of the hippocampus or olfactory bulb

vision/eye

abnormal retina ganglion cell morphology ( J:192260 )

• axonal swelling and preferential loss of smallest fibers at 14 months of age and more pronounced at 24 months of age

abnormal optic nerve morphology ( J:192260 )

• axonal swelling and preferential loss of smallest fibers at 14 months of age and more pronounced at 24 months of age

decreased a-wave amplitude ( J:192260 )

• reduced A wave amplitude in rods at 14 months of age

decreased b-wave amplitude ( J:192260 )

• reduced B wave amplitude in rods and cones at 14 months of age

abnormal eye electrophysiology ( J:192260 )

• reduced oscillatory potentials at 14 months of age

• however, mice exhibit normal visual responses as assessed by optokinetic analysis

nervous system

nervous system phenotype ( J:301716 )

N • numbers of parvalbumin, somatostatin, or neuropeptide Y interneurons in the hippocampal CA1, CA3, and dentate gyrus regions are normal

increased susceptibility to pharmacologically induced seizures ( J:301716 )

• mice exposed to a graded pharmacologic challenge with increasing exposure to flurothyl ether, a GABA-receptor antagonist, begin seizing at a lower concentration of flurothyl ether than wild-type mice, indicating mice are more susceptible to induced seizures

• however, EEG recordings do not show spontaneous seizure activity

decreased myelin sheath thickness ( J:192260 )

• in axons with abnormal mitochondria

abnormal retina ganglion cell morphology ( J:192260 )

• axonal swelling and preferential loss of smallest fibers at 14 months of age and more pronounced at 24 months of age

abnormal optic nerve morphology ( J:192260 )

• axonal swelling and preferential loss of smallest fibers at 14 months of age and more pronounced at 24 months of age

abnormal brain wave pattern ( J:301716 )

• mice exhibit differences in the resting background EEG frequency (delta, theta, alpha, beta, and gamma) power distribution throughout the 72 hours, most prominently in the low-frequency bands

• both the cortex and hippocampus have a generalized power reduction throughout the cortex and hippocampus

abnormal brain delta wave pattern ( J:301716 )

• mice show decreased delta wave power in both the cortex and hippocampus

abnormal brain theta wave pattern ( J:301716 )

• mice show decreased theta frequency power in the cortex but not the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:301716
Leber hereditary optic neuropathy		DOID:705	OMIM:535000	J:192260