Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxntm1Mkn mutation
(13 available);
any
Fxn mutation
(40 available)
|
|
|
mortality/aging
|
|
• mutant embryos exhibit early post-implantation lethality, with rapid resorption occurring during the gastrulation period
|
cellular
|
|
• 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
|
|
|
• at E6.75, many cells display nuclear and cytoplasmic features of necrosis
|
embryo
|
|
• 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
|
|
|
• at E6.75, many cells display nuclear and cytoplasmic features of necrosis
|
|
|
• mutant embryos exhibit a developmental arrest at E4.5, at the egg-cylinder stage
|
|
|
• 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
|
|
|
• 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
|
|
• 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
cellular
|
|
• mice exhibit a mitochondrial biogenesis defect, with decreases in mitochondrial copy number in brain and skeletal muscle tissue
|
mortality/aging
|
|
• 2/13 mice died during the course of the experiment; 1 of these died at about 12 months of age
|
homeostasis/metabolism
cardiovascular system
|
|
• 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)
|
|
|
• the mouse that died at ~ 12 months showed prominent heart fibrosis
|
immune system
|
|
• inflammatory arachidonic metabolites are elevated in cerebellum
|
nervous system
|
|
• inflammatory arachidonic metabolites are elevated in cerebellum
|
mortality/aging
|
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
|
|
• significant increase is observed from 9 months of age
|
nervous system
|
N |
• no neuronal histopathology is detected in cerebellar Purkinje cells or granule cells, and no abnormalities in brain or spinal cord regions are seen
|
|
|
• cerebellum shows increased induction of inflammation in response to lipopolysaccharide (LPS) treatment
|
|
|
• at 20 months, some axons in lumbar DRG display swelling and secondary demyelination
|
|
|
• some regions of lumbar DRG are devoid of cytoplasmic organelles at 20 months
|
|
|
• degenerating large DRG neurons are detected, with evidence of oxidative stress and mitochondrial dysfunction
|
|
|
• in mice >1 year of age, vacuoles are observed within the DRG in the cervical region
• 16% of cervical DRG sections display vacuoles
|
|
|
• 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
|
|
|
• slight decrease in sensory action potential in 20-months old mice is detected, suggesting a mild progressive sensory neuropathy
|
|
|
• slight decrease in sensory nerve conduction velocity in 20-months old mice is detected, suggesting a mild progressive sensory neuropathy
|
behavior/neurological
|
|
• reduced rotarod performance is exhibited by mice from 3 months of age
|
|
|
• mice show a significant decrease in locomotor activity in the open field from 6 months of age
|
cardiovascular system
|
|
• patches of lipofuscin deposition and lysosymes, with accumulation of dispersed free glycogen disrupt regular arrangement of mitochondria within cardiomyocytes at 20 months
|
cellular
|
|
• mitochondrial respiratory chain function is decreased compared to controls
|
|
|
• 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
|
|
• patches of lipofuscin deposition and lysosymes, with accumulation of dispersed free glycogen disrupt regular arrangement of mitochondria within cardiomyocytes at 20 months
|
homeostasis/metabolism
immune system
|
|
• cerebellum shows increased induction of inflammation in response to lipopolysaccharide (LPS) treatment
|
mortality/aging
|
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
|
|
• significant increase is observed from 6 months of age
|
|
|
• increase in weight from 6 months of age
|
nervous system
|
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
|
|
|
• peripheral margination of the nucleus in many large neuronal cell bodies of the dorsal root ganglia, suggesting central chromatolysis
|
|
|
• 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
|
|
|
• 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
|
|
• reduced performance on an accelerating rotarod from 3 months of age
• however, overt ataxia is not seen up to 2 years of age
|
|
|
• forelimb grip strength is decreased from 9 months of age
|
|
|
• 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
|
|
• 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
|
|
• 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
Analysis Tools