Phenotypes Associated with This Genotype

Genotype
MGI:3797844

• Allelic Composition: Fxn^tm1Mkn/Fxn^tm1Mkn; Tg(FXN)YG8Pook/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

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

mortality/aging

mortality/aging ( J:114840 )

N • embryonic lethality seen for Fxn-deficient embryos is recued by transgene expression; normal numbers of offspring are recovered and mice show normal lifespans, surviving to at least 2 years of age

growth/size/body

increased body weight ( J:114840 )

• significant increase is observed from 9 months of age

nervous system

nervous system phenotype ( J:114840 )

N • no neuronal histopathology is detected in cerebellar Purkinje cells or granule cells, and no abnormalities in brain or spinal cord regions are seen

brain inflammation ( J:216422 )

• cerebellum shows increased induction of inflammation in response to lipopolysaccharide (LPS) treatment

abnormal axon morphology ( J:114840 )

• at 20 months, some axons in lumbar DRG display swelling and secondary demyelination

chromatolysis ( J:114840 )

• some regions of lumbar DRG are devoid of cytoplasmic organelles at 20 months

neuron degeneration ( J:114840 )

• degenerating large DRG neurons are detected, with evidence of oxidative stress and mitochondrial dysfunction

abnormal dorsal root ganglion morphology ( J:114840 )

• in mice >1 year of age, vacuoles are observed within the DRG in the cervical region

• 16% of cervical DRG sections display vacuoles

abnormal lumbar dorsal root ganglion morphology ( J:114840 )

• prominent, giant vacuoles (round, singular or multiple) are observed in large sensory neuronal bodies of DRG in mice between 6 and 12 months, but not in controls; peripheral margination of nucleus in many large neuronal cell bodies with or without vacuoles

• 70% of lumbar DRG sections examined have vacuoles

abnormal action potential ( J:114840 )

• slight decrease in sensory action potential in 20-months old mice is detected, suggesting a mild progressive sensory neuropathy

decreased nerve conduction velocity ( J:114840 )

• slight decrease in sensory nerve conduction velocity in 20-months old mice is detected, suggesting a mild progressive sensory neuropathy

behavior/neurological

impaired coordination ( J:114840 )

• reduced rotarod performance is exhibited by mice from 3 months of age

decreased locomotor activity ( J:114840 )

• mice show a significant decrease in locomotor activity in the open field from 6 months of age

cardiovascular system

abnormal myocardial fiber morphology ( J:114840 )

• patches of lipofuscin deposition and lysosymes, with accumulation of dispersed free glycogen disrupt regular arrangement of mitochondria within cardiomyocytes at 20 months

cellular

abnormal respiratory electron transport chain ( J:114840 )

• mitochondrial respiratory chain function is decreased compared to controls

oxidative stress ( J:114840 )

• in 6-9 month old animals, levels of oxidized proteins are increased, most significantly in cerebrum and cerebellum, with other significant increases seen in heart and skeletal muscle

• increased lipid peroxidation is detected in heart samples

muscle

abnormal myocardial fiber morphology ( J:114840 )

• patches of lipofuscin deposition and lysosymes, with accumulation of dispersed free glycogen disrupt regular arrangement of mitochondria within cardiomyocytes at 20 months

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:114840 )

• aconitase activity is decreased to <70% of wild-type levels

immune system

brain inflammation ( J:216422 )

• cerebellum shows increased induction of inflammation in response to lipopolysaccharide (LPS) treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Friedreich ataxia		DOID:12705		J:114840 , J:216422