Phenotypes Associated with This Genotype

Genotype
MGI:5700053

• Allelic Composition: Fxn^tm1Mkn/Fxn^tm1Mkn; Tg(FXN)YG22Pook/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 6 months of age

increased susceptibility to weight gain ( J:114840 )

• increase in weight from 6 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

N • no sensory nerve or motor nerve conduction changes are seen in 9-14 month old mutants

chromatolysis ( J:114840 )

• peripheral margination of the nucleus in many large neuronal cell bodies of the dorsal root ganglia, suggesting central chromatolysis

neuron degeneration ( J:114840 )

• between 6 months to 1 year, vacuoles are seen only in the dorsal root ganglia of the lumbar region, but after 1 year, vacuoles are seen within dorsal root ganglia of the cervical region, indicating a distal-to-proximal dying back neurodegeneration

abnormal dorsal root ganglion morphology ( J:114840 )

• prominent, giant vacuoles (round, singular or multiple) are observed in large sensory neuronal bodies of dorsal root ganglia; peripheral margination of nucleus in many large neuronal cell bodies with or without vacuoles

behavior/neurological

impaired coordination ( J:114840 )

• reduced performance on an accelerating rotarod from 3 months of age

• however, overt ataxia is not seen up to 2 years of age

decreased grip strength ( J:114840 )

• forelimb grip strength is decreased from 9 months of age

decreased locomotor activity ( J:114840 )

• mice show a decreased trend in locomotor activity in the open field from 6 months of age and a significant difference by 1 year of age

cardiovascular system

increased heart iron level ( J:114840 )

• iron deposition within the heart of 14-18 month old mice

• however, mice do not exhibit an increase in heart weight to body weight ratio, myofibril disarray, or fibrosis

cellular

oxidative stress ( J:114840 )

• in 6-9 month old mice, oxidized proteins are increased in the cerebrum, cerebellum, heart, and skeletal muscle, with the most prominent increase in the cerebrum and cerebellum

• increase in lipid peroxidation in the heart

homeostasis/metabolism

increased heart iron level ( J:114840 )

• iron deposition within the heart of 14-18 month old mice

• however, mice do not exhibit an increase in heart weight to body weight ratio, myofibril disarray, or fibrosis

abnormal enzyme/coenzyme level ( J:114840 )

• level of the antioxidant enzyme CuZnSOD is decreased in the skeletal muscle by 40%

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