All Phenotypes Fxn<tm1Mkn> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fxn^tm1Mkn/Fxn^tm1Mkn	involves: 129 * C57BL/6J	MGI:2177163
ht2	Fxn^tm1.1Pand/Fxn^tm1Mkn	B6.Cg-Fxn^tm1.1Pand Fxn^tm1Mkn/J	MGI:6101473
ht3	Fxn^tm1Mkn/Fxn^tm1Pand	involves: 129/Sv * C57BL/6	MGI:3652375
cx4	Fxn^tm1Mkn/Fxn^tm1Mkn Tg(FXN)YG8Pook/0	involves: 129/Sv * C57BL/6 * CBA	MGI:3797844
cx5	Fxn^tm1Mkn/Fxn^tm1Mkn Tg(FXN)YG22Pook/0	involves: 129/Sv * C57BL/6 * CBA	MGI:5700053

Allelic Composition	Fxn^tm1Mkn/Fxn^tm1Mkn
Genetic Background	involves: 129 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxn^tm1Mkn mutation (14 available); any Fxn mutation (42 available)

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

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:62185 )

• mutant embryos exhibit early post-implantation lethality, with rapid resorption occurring during the gastrulation period

cellular

increased embryonic tissue cell apoptosis ( J:62185 )

• at E6.75 and E7.5, cells with pycnotic nuclei and condensed chromatin are detected throughout the mutant embryos

• TUNEL-positive apoptotic cells are most abundant in the extra-embryonic region of E6.75 and E7.5 mutant embryos

embryo

increased embryonic tissue cell apoptosis ( J:62185 )

• at E6.75 and E7.5, cells with pycnotic nuclei and condensed chromatin are detected throughout the mutant embryos

• TUNEL-positive apoptotic cells are most abundant in the extra-embryonic region of E6.75 and E7.5 mutant embryos

embryonic growth arrest ( J:62185 )

• mutant embryos exhibit a developmental arrest at E4.5, at the egg-cylinder stage

decreased embryo size ( J:62185 )

• at E7.5, mutant embryos are smaller and grossly abnormal relative to wild-type

• at E8.5 and E9.5, mutant embryos undergo resorption and are reduced to small masses of haemorrhagic tissue

embryo tissue necrosis ( J:62185 )

• at E6.75, many cells display nuclear and cytoplasmic features of necrosis

abnormal extraembryonic tissue morphology ( J:62185 )

• during resorption, the extraembryonic region of the conceptus is severely reduced and lacks distinct exocoelomic and chorionic cavities

• in contrast, the ectodermal, mesodermal and endodermal cell layers remain relatively unaffected

growth/size/body

decreased embryo size ( J:62185 )

• at E7.5, mutant embryos are smaller and grossly abnormal relative to wild-type

• at E8.5 and E9.5, mutant embryos undergo resorption and are reduced to small masses of haemorrhagic tissue

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:62185 )

N	• Perls staining indicates absence of iron-specific staining in mutant E6.5-E8.5 embryos • also, no iron deposits are detected in resorbed E6.75 embryos, either in mitochondria or in the cytosol, suggesting that cell death is not due to abnormal iron accumulation

Allelic Composition	Fxn^tm1.1Pand/Fxn^tm1Mkn
Genetic Background	B6.Cg-Fxn^tm1.1Pand Fxn^tm1Mkn/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxn^tm1.1Pand mutation (2 available); any Fxn mutation (42 available)
Fxn^tm1Mkn mutation (14 available); any Fxn mutation (42 available)

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

cellular

abnormal mitochondrial biogenesis ( J:242978 )

• mice exhibit a mitochondrial biogenesis defect, with decreases in mitochondrial copy number in brain and skeletal muscle tissue

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Friedreich ataxia		DOID:12705		J:242978

Allelic Composition	Fxn^tm1Mkn/Fxn^tm1Pand
Genetic Background	involves: 129/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxn^tm1Mkn mutation (14 available); any Fxn mutation (42 available)
Fxn^tm1Pand mutation (2 available); any Fxn mutation (42 available)

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

mortality/aging

premature death ( J:109164 )

• 2/13 mice died during the course of the experiment; 1 of these died at about 12 months of age

homeostasis/metabolism

increased heart iron level ( J:109164 )

• the mouse that died at about 12 months of age had 3-fold higher iron levels in the heart than littermates (1168 ug vs 399 ug)

cardiovascular system

increased heart iron level ( J:109164 )

• the mouse that died at about 12 months of age had 3-fold higher iron levels in the heart than littermates (1168 ug vs 399 ug)

cardiac fibrosis ( J:109164 )

• the mouse that died at ~ 12 months showed prominent heart fibrosis

immune system

brain inflammation ( J:216422 )

• inflammatory arachidonic metabolites are elevated in cerebellum

nervous system

brain inflammation ( J:216422 )

• inflammatory arachidonic metabolites are elevated in cerebellum

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

♀	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

Allelic Composition	Fxn^tm1Mkn/Fxn^tm1Mkn Tg(FXN)YG22Pook/0
Genetic Background	involves: 129/Sv * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxn^tm1Mkn mutation (14 available); any Fxn mutation (42 available)
Tg(FXN)YG22Pook mutation (2 available)

♀	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 • 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

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