Phenotypes Associated with This Genotype

Genotype
MGI:2177208

• Allelic Composition: Fxn^tm2Mkn/Fxn^tm2.1Mkn; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129 * C57BL/6J

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

mortality/aging

premature death ( J:75420 )

• mutant mice die at 24 9 days after birth

behavior/neurological

abnormal motor coordination/balance ( J:75420 )

• mutant mice display loss of proprioception, as shown by the mis-positioning of the right hind-paw, which the mouse fails to perceive

ataxia ( J:75420 )

• mutant mice exhibit an average onset of ataxia at 12 days after birth

hunched posture ( J:75420 )

abnormal gait ( J:75420 )

• mutant mice develop a rapidly progressive gait abnormality

growth/size/body

cardiac hypertrophy ( J:75420 )

• at 2-3 weeks of age (shortly before or at death), mutants show a significantly increased mean heart to body weight ratio relative to wild-type mice (13.7 6 mg/g vs 5.8 0.5 mg/g, respectively)

decreased body weight ( J:75420 )

• mutant mice exhibit a low birth weight

weight loss ( J:75420 )

• mutants mice show progressive weight loss, with a 18% and 41% weight reduction noted at 7 days after birth and at death, respectively

• by P16, most mutants are moribund and rapidly stop gaining weight; some even rapidly lose weight

decreased body length ( J:75420 )

• at P12, mutants display reduced body length relative to wild-type mice; however, no obvious skeletal abnormalities are observed

postnatal growth retardation ( J:75420 )

• mutant mice display reduced growth rates throughout their lifespan relative to wild-type mice

muscle

muscle phenotype ( J:75420 )

N

abnormal myocardial fiber morphology ( J:75420 )

• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae

myocardium necrosis ( J:75420 )

dilated cardiomyopathy ( J:75420 )

cardiovascular system

abnormal myocardial fiber morphology ( J:75420 )

• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae

myocardium necrosis ( J:75420 )

cardiac hypertrophy ( J:75420 )

• at 2-3 weeks of age (shortly before or at death), mutants show a significantly increased mean heart to body weight ratio relative to wild-type mice (13.7 6 mg/g vs 5.8 0.5 mg/g, respectively)

cardiac fibrosis ( J:75420 )

dilated cardiomyopathy ( J:75420 )

cellular

dilated mitochondrion ( J:75420 )

• at 2 weeks, 50% of cardiac mitochondria appear to be swollen in the myofibrils

nervous system

neurodegeneration ( J:75420 )

• mutants exhibit areas of degeneration and necrosis in the dentate nucleus of the cerebellum and the brainstem (esp. in the trigeminal nucleus and tracts, the vestibular system and the cochlear nuclei and nerve)

• in contrast, the spinal cord, dorsal root ganglia and peripheral nerves appear unaffected

spongiform encephalopathy ( J:75420 )

abnormal nerve conduction ( J:75420 )

• upon electromyography, mutants show specific absence of the spinal somatosensory evoked response (H band), indicating a dysfunction in the large myelinated proprioceptive sensory neurons

• in contrast, the small myelinated sensory axons of the tail (heat and pain) have normal velocity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Friedreich ataxia		DOID:12705		J:75420