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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 10 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
Cnptm1(cre)Kan/Cnp+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ MGI:5749838
cn5
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:5292515
cn6
Myl1tm1(cre)Sjb/Myl1+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:2450161
cn7
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Camk2a-cre)1Lfr/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA MGI:2177642
cn8
Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA MGI:2177640
cn9
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL MGI:3702932
cn10
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 (343 available)
Park2tm1Roo mutation (0 available); any Park2 mutation (20 available)
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (38 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 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
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
• however, mitochondria in the distal dopamine axons are morphologically spared
• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells




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 (38 available)
Sncatm1Nbm mutation (5 available); any Snca mutation (17 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 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




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 (6 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

growth/size/body
• cessation of weight gain from P10 onwards

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

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

behavior/neurological
• decreased spontaneous movement from P10 onwards

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

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

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




Genotype
MGI:5749838
cn4
Allelic
Composition
Cnptm1(cre)Kan/Cnp+
Tfamtm1Lrsn/Tfamtm1Lrsn
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnptm1(cre)Kan mutation (0 available); any Cnp mutation (13 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most mice die by 12 weeks of age

nervous system
• in the proximal and distal small intestine at 2 and 7 weeks
• however, the number of enteric neurons in the colon is not significantly different
• in the proximal and distal small intestine at 2 and 7 weeks
• however, the number of glia in the colon is not significantly different
• loss of nitrergic inhibitory neuron
• profound in more proximal regions of the small intestine
• of enteric neurons in proximal and distal small intestine

growth/size/body
• after 2 weeks of age
• after 2 weeks of age
• at about 6 to 8 weeks of age

digestive/alimentary system
• small diameter colon
• massive dilation within the proximal small bowel with dark-colored luminal content and relative contraction of the distal small bowel with no stool pellets in the colon or rectum
• small diameter small intestine
• however, no stenosis or mechanical cause of the obstruction is evident

cellular
• in enteric neurons and glia




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 (343 available)
Slc6a3tm1(cre)Lrsn mutation (0 available); any Slc6a3 mutation (38 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 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
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells

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

behavior/neurological
• impaired from 20 weeks of age

growth/size/body
• from 20 weeks of age

muscle
• rigidity from 20 weeks of age




Genotype
MGI:2450161
cn6
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 (5 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 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

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

cellular
• respiratory chain dysfunction in skeletal muscle

behavior/neurological
• from 3-4 months of age

growth/size/body
• beginning at 4-5 months of age




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 (6 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

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

cellular
• resipratory chain dysfunction in neurons of the neocortex and hippocampus




Genotype
MGI:2177640
cn8
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 (6 available)
Tg(Ins2-cre)25Mgn mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• decreased blood insulin concentration, onset at 5 week of age
• onset at 27-33 weeks

endocrine/exocrine glands
• normal numbers at 7 weeks, absent at 37 weeks

cellular
• mitochondrial DNA depletion
• respiratory chain dysfunction in pancreatic islets




Genotype
MGI:3702932
cn9
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 (38 available)
Tfamtm1Lrsn mutation (0 available); any Tfam mutation (6 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

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

nervous system
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks
• majority of neurons contain small cytoplasmic aggregates, detected at 6 weeks through 43 weeks
• inclusions are present in most dopaminergic midbrain neurons and the mean size increased as the neurodegeneration progressed
• 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
• 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
• 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

muscle
• twitching is observed at 20 weeks of age

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

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




Genotype
MGI:2177637
cn10
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 (6 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
• animals surviving past neonatal stage survive for several months; variable penetrance speculated to be the result of a modifying gene

cardiovascular system

cellular
• respiratory chain dysfunction in heart; variable penetrance speculated to be the result of a modifying gene

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





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last database update
11/29/2016
MGI 6.06
The Jackson Laboratory