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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tfamtm1Lrsn
targeted mutation 1, Nils-Goran Larsson
MGI:1860962
Summary 9 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Park2tm1Roo/Park2tm1Roo
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 MGI:5292517
cn2
Slc6a3tm1(cre)Lrsn/Slc6a3+
Sncatm1Nbm/Sncatm1Nbm
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL MGI:3702933
cn3
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ckmm-cre)1Lrsn/0
involves: 129S1/Sv * 129X1/SvJ MGI:2177634
cn4
Myl1tm1(cre)Sjb/Myl1+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:2450161
cn5
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:5292515
cn6
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA MGI:2177640
cn7
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Camk2a-cre)1Lfr/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA MGI:2177642
cn8
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL MGI:3702932
cn9
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Myhca-cre)1Lrsn/0
involves: 129S1/Sv * 129X1/SvJ * FVB MGI:2177637


Genotype
MGI:5292517
cn1
Allelic
Composition
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Park2tm1Roo/Park2tm1Roo
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Lrsn mutation (0 available); any Gt(ROSA)26Sor mutation (305 available)
Park2tm1Roo mutation (0 available); any Park2 mutation (12 available)
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (14 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus (J:176022)
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells (J:176022)
• however, mitochondria in the distal dopamine axons are morphologically spared (J:176022)
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus (J:176022)
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells (J:176022)
• however, mitochondria in the distal dopamine axons are morphologically spared (J:176022)
• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells (J:176022)
• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells (J:176022)




Genotype
MGI:3702933
cn2
Allelic
Composition
Slc6a3tm1(cre)Lrsn/Slc6a3+
Sncatm1Nbm/Sncatm1Nbm
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (14 available)
Sncatm1Nbm mutation (5 available); any Snca mutation (15 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• triple mutants show same phenotype as Tfamtm1Lrsn, Slc6a3tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype (J:119515)
• triple mutants show same phenotype as Tfamtm1Lrsn, Slc6a3tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype (J:119515)




Genotype
MGI:2177634
cn3
Allelic
Composition
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ckmm-cre)1Lrsn/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
Tg(Ckmm-cre)1Lrsn mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Heart histology of Tfamtm1Lrsn/Tfamtm1Lrsn Tg(Ckmm-cre)1Lrsn/0 mice

mortality/aging
• die at 2-4 weeks of age (J:51964)
• die at 2-4 weeks of age (J:51964)

growth/size/body
• cessation of weight gain from P10 onwards (J:51964)
• cessation of weight gain from P10 onwards (J:51964)

cardiovascular system
• dilated (J:51964)
• dilated (J:51964)
• ECG changes under isofluorane anesthesia (J:51964)
• ECG changes under isofluorane anesthesia (J:51964)
• decrease in peak aortic blood flow velocity under isofluorane anesthesia (J:51964)
• decrease in peak aortic blood flow velocity under isofluorane anesthesia (J:51964)
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)

homeostasis/metabolism
• levels of aconitase, a mitochondrial enzyme, and nucleus-encoded respiratory chain complex II are not affected (J:125471)
• levels of aconitase, a mitochondrial enzyme, and nucleus-encoded respiratory chain complex II are not affected (J:125471)
• total glutathione peroxidase enzyme activity is elevated in hearts (J:125471)
• total glutathione peroxidase enzyme activity is elevated in hearts (J:125471)
• ECG changes under isofluorane anesthesia (J:51964)
• decrease in peak aortic blood flow velocity under isofluorane anesthesia (J:51964)
• ECG changes under isofluorane anesthesia (J:51964)
• decrease in peak aortic blood flow velocity under isofluorane anesthesia (J:51964)

behavior/neurological
• decreased spontaneous movement from P10 onwards (J:51964)
• decreased spontaneous movement from P10 onwards (J:51964)

muscle
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)

cellular
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)
• mutants exhibit a significant increase in apoptosis of cardiomyocytes (J:125471)
• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts (J:125471)
• mosaic respiratory chain deficiency in the myocardium (J:125471)
• mosaic respiratory chain deficiency in the myocardium (J:125471)

Mouse Models of Human Disease
OMIM ID Ref(s)
Kearns-Sayre Syndrome; KSS 530000 J:51964




Genotype
MGI:2450161
cn4
Allelic
Composition
Myl1tm1(cre)Sjb/Myl1+
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myl1tm1(cre)Sjb mutation (1 available); any Myl1 mutation (3 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Skeletal muscle analysis of Tfamtm1Lrsn/Tfamtm1Lrsn Myl1tm1(cre)Sjb/Myl1+ mice

mortality/aging
• death occurs at 4-5 months of age (J:81561)
• death occurs at 4-5 months of age (J:81561)

muscle
• increased muscle fiber size containing enlarged mitochondria with distorted cristae (J:81561)
• increased muscle fiber size containing enlarged mitochondria with distorted cristae (J:81561)
• shorter contraction times and shorter twitch-relaxation times (J:81561)
• decreased absolute muscle force (J:81561)
• shorter contraction times and shorter twitch-relaxation times (J:81561)
• decreased absolute muscle force (J:81561)

cellular
• respiratory chain dysfunction in skeletal muscle (J:81561)
• respiratory chain dysfunction in skeletal muscle (J:81561)

behavior/neurological
• from 3-4 months of age (J:81561)
• from 3-4 months of age (J:81561)

growth/size/body
• beginning at 4-5 months of age (J:81561)
• beginning at 4-5 months of age (J:81561)




Genotype
MGI:5292515
cn5
Allelic
Composition
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Lrsn mutation (0 available); any Gt(ROSA)26Sor mutation (305 available)
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (14 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Mitochondria abnormalities in Tfamtm1Lrsn/Tfamtm1Lrsn Slc6a3tm1(cre)Lrsn/Slc6a3+ Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ neurons

nervous system
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus (J:176022)
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells (J:176022)
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus (J:176022)
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells (J:176022)

cellular
• smaller mitochondrial and the largest aggregates in a rare number of neurons exhibit reduced import competence compared with mitochondria in control cells (J:176022)
• smaller mitochondrial and the largest aggregates in a rare number of neurons exhibit reduced import competence compared with mitochondria in control cells (J:176022)

behavior/neurological
• impaired from 20 weeks of age (J:176022)
• impaired from 20 weeks of age (J:176022)

growth/size/body
• from 20 weeks of age (J:176022)
• from 20 weeks of age (J:176022)

muscle
• rigidity from 20 weeks of age (J:176022)
• rigidity from 20 weeks of age (J:176022)




Genotype
MGI:2177640
cn6
Allelic
Composition
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ins2-cre)25Mgn/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
Tg(Ins2-cre)25Mgn mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• impaired (J:65522)
• impaired (J:65522)
• decreased blood insulin concentration, onset at 5 week of age (J:65522)
• decreased blood insulin concentration, onset at 5 week of age (J:65522)
• onset at 27-33 weeks (J:65522)
• onset at 27-33 weeks (J:65522)

endocrine/exocrine glands
• normal numbers at 7 weeks, absent at 37 weeks (J:65522)
• normal numbers at 7 weeks, absent at 37 weeks (J:65522)
• impaired (J:65522)
• impaired (J:65522)

cellular
• mitochondrial DNA depletion (J:65522)
• mitochondrial DNA depletion (J:65522)
• respiratory chain dysfunction in pancreatic islets (J:65522)
• respiratory chain dysfunction in pancreatic islets (J:65522)




Genotype
MGI:2177642
cn7
Allelic
Composition
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Camk2a-cre)1Lfr/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
Tg(Camk2a-cre)1Lfr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• at 5-6 months of age, preceded by 1-2 weeks of rapid physical deterioration (J:72037)
• at 5-6 months of age, preceded by 1-2 weeks of rapid physical deterioration (J:72037)

nervous system
• in corpus callosum, hippocampus; progressive with age (J:72037)
• in corpus callosum, hippocampus; progressive with age (J:72037)
• degeneration of cortical organization in neocortex (J:72037)
• degeneration of cortical organization in neocortex (J:72037)
• neuronal apoptosis in neocortex and hippocampus; progressive with age (J:72037)
• neuronal apoptosis in neocortex and hippocampus; progressive with age (J:72037)

cellular
• resipratory chain dysfunction in neurons of the neocortex and hippocampus (J:72037)
• resipratory chain dysfunction in neurons of the neocortex and hippocampus (J:72037)




Genotype
MGI:3702932
cn8
Allelic
Composition
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (14 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants have to be terminated at ~45 weeks due to poor general condition (J:119515)
• mutants have to be terminated at ~45 weeks due to poor general condition (J:119515)

behavior/neurological
• mice aged 14-15 weeks display decreased exploratory activity (J:119515)
• mice aged 14-15 weeks display decreased exploratory activity (J:119515)
• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age (J:119515)
• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age (J:119515)
• apparent limb rigidity is observed at 20 weeks of age (J:119515)
• apparent limb rigidity is observed at 20 weeks of age (J:119515)

nervous system
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice (J:119515)
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks (J:119515)
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice (J:119515)
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks (J:119515)
• majority of neurons contain small cytoplasmic aggregates, detected at 6 weeks through 43 weeks (J:119515)
• inclusions are present in most dopaminergic midbrain neurons and the mean size increased as the neurodegeneration progressed (J:119515)
• large, partially electron-dense bodies located in dendritic structures close to neuronal somata are observed at 11 weeks; some of these bodies have an amorphous content with a diffuse lining, while others display tubular formations and have distinct double layer membranes which are ultrastructurally typical of mitochondrial membranes (J:119515)
• majority of neurons contain small cytoplasmic aggregates, detected at 6 weeks through 43 weeks (J:119515)
• inclusions are present in most dopaminergic midbrain neurons and the mean size increased as the neurodegeneration progressed (J:119515)
• large, partially electron-dense bodies located in dendritic structures close to neuronal somata are observed at 11 weeks; some of these bodies have an amorphous content with a diffuse lining, while others display tubular formations and have distinct double layer membranes which are ultrastructurally typical of mitochondrial membranes (J:119515)
• dopaminergic (DA) neuron loss is observed in the dorsolateral striatum at 12 weeks of age, progressing to involve most of the dorsal and ventral striatum with age (J:119515)
• tyrosine hydroxylase-expressing midbrain neurons show a slow progressive cell loss, which is more marked and starts sooner in the substantia nigra compared to the ventral tegmental area (J:119515)
• dopaminergic (DA) neuron loss is observed in the dorsolateral striatum at 12 weeks of age, progressing to involve most of the dorsal and ventral striatum with age (J:119515)
• tyrosine hydroxylase-expressing midbrain neurons show a slow progressive cell loss, which is more marked and starts sooner in the substantia nigra compared to the ventral tegmental area (J:119515)

muscle
• twitching is observed at 20 weeks of age (J:119515)
• twitching is observed at 20 weeks of age (J:119515)

homeostasis/metabolism
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice (J:119515)
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks (J:119515)
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice (J:119515)
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks (J:119515)

Mouse Models of Human Disease
OMIM ID Ref(s)
Parkinson Disease, Mitochondrial 556500 J:119515




Genotype
MGI:2177637
cn9
Allelic
Composition
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Myhca-cre)1Lrsn/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (4 available)
Tg(Myhca-cre)1Lrsn mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 75% of animals die as neonates (J:61372)
• 75% of animals die as neonates (J:61372)
• animals surviving past neonatal stage survive for several months; variable penetrance speculated to be the result of a modifying gene (J:61372)
• animals surviving past neonatal stage survive for several months; variable penetrance speculated to be the result of a modifying gene (J:61372)

cardiovascular system

cellular
• respiratory chain dysfunction in heart; variable penetrance speculated to be the result of a modifying gene (J:61372)
• respiratory chain dysfunction in heart; variable penetrance speculated to be the result of a modifying gene (J:61372)

Mouse Models of Human Disease
OMIM ID Ref(s)
Kearns-Sayre Syndrome; KSS 530000 J:61372





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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory