Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(942 available)
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normal phenotype
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• mice are viable and fertile
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mortality/aging
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• mutants die around 6-7 weeks of age due to malnutrition; this is most likely due to difficulty accessing food and water in normal cages due to a rearing defect
• however, when mutants are supplied with hydrated gel packs and crushed pieces of regular chow, all mutants survive beyond 6 months of age, with a majority surviving past 1 year of age
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growth/size/body
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• mutants are significantly smaller than controls by 5 weeks of age
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• mutants do not gain weight after 4 weeks of age
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behavior/neurological
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• mutants are hunched by 5 weeks of age
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• severe rearing defect as early as 4 weeks of age
• treatment of mutants with L-DOPA alleviates the motor defects
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• mutants are hypoactive by 5 weeks of age
• at 4-5 weeks of age, mutants travel only 68% of the distance traveled by wild-type mice and by 8-11 weeks of age, the distance traveled reduces to 34% of wild-type, indicating an age-dependent decline in locomotive activity
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• beginning at 4-5 weeks, mutants exhibit progressive bradykinesia
• mutants exhibit a decline in the speed of movement with age compared to controls
• mutants spend twice as much time inactive at 6-7 weeks of age as controls and by 8-11 weeks of age, this increases to 6-fold increase in inactive time
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nervous system
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• loss of dopaminergic terminals in the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and 76% reduction by 8-10 weeks
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• mutants exhibit loss of dopaminergic efferents to the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and a 76% reduction by 8-10 weeks of age
• however, projections to the nucleus accumbens and olfactory tubercle are protected and the dopaminergic terminals are moderately preserved at 11-14 weeks
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• dopaminergic neurons remaining have smaller cell bodies and diminished neuronal processes
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
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• retrograde degeneration of substantia nigra pars compacta dopaminergic neurons and to a lesser extent in the mesolimbic pathway
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• progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit, with neuronal loss first seen at 10-12 weeks, when a 52% decrease in TH-positive neurons is seen
• some degeneration is also seen in the mesolimbic pathway, although a lesser extent than in the nigrostriatal circuit
• degeneration of dopaminergic neurons occurs in a stepwise manner, with initial defects at the axon terminals, followed 1-2 months later by degeneration of the cell bodies
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• mutants show decreased mitochondrial transport along nerve processes
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cellular
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• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
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skeleton
normal phenotype
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• mice show no abnormal phenotype up to 1 year of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fis1tm1.1Dcc mutation
(0 available);
any
Fis1 mutation
(47 available)
Fis1tm1Dcc mutation
(0 available);
any
Fis1 mutation
(47 available)
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(942 available)
Tg(Stra8-icre)1Reb mutation
(2 available)
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reproductive system
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• no spermatozoa in epididymides
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• impaired acrosome development and failure to produce elongated spermatids
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• with increased mitochondria content
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• 4-fold increase in tubules
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cellular
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• no spermatozoa in epididymides
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• impaired acrosome development and failure to produce elongated spermatids
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• with increased mitochondria content
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• in round spermatids and giant cells
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• in round spermatids and giant cells with aberrant accumulation of autophagic structures
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• 4-fold increase in tubules
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homeostasis/metabolism
endocrine/exocrine glands
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(942 available)
MffGt(AZ0438)Wtsi mutation
(1 available);
any
Mff mutation
(25 available)
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reproductive system
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• >5% of caudal epididymidal sperm contain kinks in the neck
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• >15% of caudal epididymidal sperm contain kinks in the midpiece
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• caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles
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• >40% of caudal epididymidal sperm contain kinks in the principal piece
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• >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck
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• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
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• caudal epididymidal sperm are significantly less motile than wild-type sperm
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• in an in vitro fertilization assay, cauda epididymidal sperm failed to fertilize any oocytes
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cellular
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• >5% of caudal epididymidal sperm contain kinks in the neck
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• >15% of caudal epididymidal sperm contain kinks in the midpiece
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• caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles
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• >40% of caudal epididymidal sperm contain kinks in the principal piece
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• >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck
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• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
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• most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented
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• total mito-Dendra2 fluorescence is markedly reduced in the midpiece of epididymidal sperm
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• caudal epididymidal sperm are significantly less motile than wild-type sperm
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Analysis Tools