All Phenotypes Tfam<tm1Lrsn> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Tfam^tm1Lrsn
targeted mutation 1, Nils-Goran Larsson
MGI:1860962

Summary

10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺ Prkn^tm1Roo/Prkn^tm1Roo Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:5292517
cn2	Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Snca^tm1Nbm/Snca^tm1Nbm Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL	MGI:3702933
cn3	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Ckmm-cre)1Lrsn/0	involves: 129S1/Sv * 129X1/SvJ	MGI:2177634
cn4	Cnp^tm1(cre)Kan/Cnp⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129X1/SvJ	MGI:5749838
cn5	Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺ Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5292515
cn6	Myl1^tm1(cre)Sjb/Myl1⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2450161
cn7	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Camk2a-cre)1Lfr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:2177642
cn8	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:2177640
cn9	Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3702932
cn10	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Myhca-cre)1Lrsn/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:2177637

Allelic Composition	Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺ Prkn^tm1Roo/Prkn^tm1Roo Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn
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)26Sor^tm1Lrsn mutation (1 available); any Gt(ROSA)26Sor mutation (993 available)
Prkn^tm1Roo mutation (0 available); any Prkn mutation (54 available)
Slc6a3^tm1(cre)Lrsn mutation (1 available); any Slc6a3 mutation (66 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

nervous system

abnormal neuron morphology ( 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

• 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

loss of dopaminergic neurons ( J:176022 )

abnormal axonal transport ( 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

Allelic Composition	Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Snca^tm1Nbm/Snca^tm1Nbm Tfam^tm1Lrsn/Tfam^tm1Lrsn
Genetic Background	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3^tm1(cre)Lrsn mutation (1 available); any Slc6a3 mutation (66 available)
Snca^tm1Nbm mutation (5 available); any Snca mutation (36 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

nervous system

neuronal intranuclear inclusions ( J:119515 )

• triple mutants show same phenotype as Tfam^tm1Lrsn, Slc6a3^tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype

Allelic Composition	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Ckmm-cre)1Lrsn/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)
Tg(Ckmm-cre)1Lrsn mutation (0 available)

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

Heart histology of Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Ckmm-cre)1Lrsn/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:51964 )

• die at 2-4 weeks of age

growth/size/body

enlarged heart ( J:51964 )

• dilated

increased heart weight ( J:51964 )

postnatal growth retardation ( J:51964 )

• cessation of weight gain from P10 onwards

cardiovascular system

enlarged heart ( J:51964 )

• dilated

increased heart weight ( J:51964 )

dilated heart left ventricle ( J:51964 )

abnormal cardiovascular system physiology ( J:51964 )

• ECG changes under isofluorane anesthesia

dilated cardiomyopathy ( J:51964 )

abnormal blood flow velocity ( J:51964 )

• decrease in peak aortic blood flow velocity under isofluorane anesthesia

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:125471 )

• levels of aconitase, a mitochondrial enzyme, and nucleus-encoded respiratory chain complex II are not affected

increased glutathione peroxidase activity ( J:125471 )

• total glutathione peroxidase enzyme activity is elevated in hearts

increased physiological sensitivity to xenobiotic ( J:51964 )

• ECG changes under isofluorane anesthesia

• decrease in peak aortic blood flow velocity under isofluorane anesthesia

behavior/neurological

bradykinesia ( J:51964 )

• decreased spontaneous movement from P10 onwards

muscle

dilated cardiomyopathy ( J:51964 )

increased cardiomyocyte apoptosis ( J:125471 )

• 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

increased cardiomyocyte apoptosis ( J:125471 )

• mutants exhibit a significant increase in apoptosis of cardiomyocytes

• however, no evidence of fibrosis, necrosis, or inflammatory cell infiltration is seen in the hearts

abnormal respiratory electron transport chain ( J:125471 )

• mosaic respiratory chain deficiency in the myocardium

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Kearns-Sayre syndrome		DOID:12934	OMIM:530000	J:51964

Allelic Composition	Cnp^tm1(cre)Kan/Cnp⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnp^tm1(cre)Kan mutation (0 available); any Cnp mutation (27 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

mortality/aging

premature death ( J:228933 )

• most mice die by 12 weeks of age

nervous system

decreased neuron mitochondrial DNA content ( J:228933 )

abnormal enteric neuron morphology ( J:228933 )

• 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

abnormal PNS glial cell morphology ( J:228933 )

• in the proximal and distal small intestine at 2 and 7 weeks

• however, the number of glia in the colon is not significantly different

decreased neuron number ( J:228933 )

• loss of nitrergic inhibitory neuron

neurodegeneration ( J:228933 )

• profound in more proximal regions of the small intestine

axon degeneration ( J:228933 )

• of enteric neurons in proximal and distal small intestine

growth/size/body

decreased body size ( J:228933 )

• after 2 weeks of age

postnatal growth retardation ( J:228933 )

• after 2 weeks of age

distended abdomen ( J:228933 )

• at about 6 to 8 weeks of age

digestive/alimentary system

abnormal colon morphology ( J:228933 )

• small diameter colon

abnormal small intestine morphology ( J:228933 )

• 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

decreased mitochondrial DNA content ( J:228933 )

• in enteric neurons and glia

decreased neuron mitochondrial DNA content ( J:228933 )

Allelic Composition	Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺ Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^tm1Lrsn mutation (1 available); any Gt(ROSA)26Sor mutation (993 available)
Slc6a3^tm1(cre)Lrsn mutation (1 available); any Slc6a3 mutation (66 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

Mitochondria abnormalities in Tfam^tm1Lrsn/Tfam^tm1Lrsn Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺ neurons

nervous system

abnormal neuron morphology ( J:176022 )

• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells

loss of dopaminergic neurons ( J:176022 )

cellular

abnormal mitochondrial physiology ( J:176022 )

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

behavior/neurological

abnormal locomotor behavior ( J:176022 )

• impaired from 20 weeks of age

growth/size/body

weight loss ( J:176022 )

• from 20 weeks of age

muscle

muscle hypertonia ( J:176022 )

• rigidity from 20 weeks of age

Allelic Composition	Myl1^tm1(cre)Sjb/Myl1⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myl1^tm1(cre)Sjb mutation (2 available); any Myl1 mutation (17 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

Skeletal muscle analysis of Tfam^tm1Lrsn/Tfam^tm1Lrsn Myl1^tm1(cre)Sjb/Myl1⁺ mice

mortality/aging

premature death ( J:81561 )

• death occurs at 4-5 months of age

muscle

increased skeletal muscle fiber size ( J:81561 )

• increased muscle fiber size containing enlarged mitochondria with distorted cristae

impaired skeletal muscle contractility ( J:81561 )

• shorter contraction times and shorter twitch-relaxation times

• decreased absolute muscle force

cellular

abnormal respiratory electron transport chain ( J:81561 )

• respiratory chain dysfunction in skeletal muscle

behavior/neurological

bradykinesia ( J:81561 )

• from 3-4 months of age

growth/size/body

weight loss ( J:81561 )

• beginning at 4-5 months of age

Allelic Composition	Tfam^tm1Lrsn/Tfam^tm1Lrsn 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:
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)
Tg(Camk2a-cre)1Lfr mutation (2 available)

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

mortality/aging

premature death ( J:72037 )

• at 5-6 months of age, preceded by 1-2 weeks of rapid physical deterioration

nervous system

gliosis ( J:72037 )

• in corpus callosum, hippocampus; progressive with age

neurodegeneration ( J:72037 )

• degeneration of cortical organization in neocortex

neuron degeneration ( J:72037 )

• neuronal apoptosis in neocortex and hippocampus; progressive with age

axon degeneration ( J:72037 )

cellular

abnormal respiratory electron transport chain ( J:72037 )

• resipratory chain dysfunction in neurons of the neocortex and hippocampus

Allelic Composition	Tfam^tm1Lrsn/Tfam^tm1Lrsn 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:
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)
Tg(Ins2-cre)25Mgn mutation (2 available)

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

homeostasis/metabolism

decreased insulin secretion ( J:65522 )

• impaired

abnormal circulating insulin level ( J:65522 )

• decreased blood insulin concentration, onset at 5 week of age

increased insulin sensitivity ( J:65522 )

• onset at 27-33 weeks

endocrine/exocrine glands

absent pancreatic beta cells ( J:65522 )

• normal numbers at 7 weeks, absent at 37 weeks

decreased insulin secretion ( J:65522 )

• impaired

cellular

abnormal mitochondrial morphology ( J:65522 )

decreased mitochondrial DNA content ( J:65522 )

• mitochondrial DNA depletion

abnormal respiratory electron transport chain ( J:65522 )

• respiratory chain dysfunction in pancreatic islets

Allelic Composition	Slc6a3^tm1(cre)Lrsn/Slc6a3⁺ Tfam^tm1Lrsn/Tfam^tm1Lrsn
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3^tm1(cre)Lrsn mutation (1 available); any Slc6a3 mutation (66 available)
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)

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

mortality/aging

premature death ( J:119515 )

• mutants have to be terminated at ~45 weeks due to poor general condition

behavior/neurological

decreased exploration in new environment ( J:119515 )

• mice aged 14-15 weeks display decreased exploratory activity

tremors ( J:119515 )

• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age

abnormal limb posture ( J:119515 )

• apparent limb rigidity is observed at 20 weeks of age

decreased locomotor activity ( J:119515 )

nervous system

abnormal dopaminergic neuron morphology ( J:119515 )

• 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

loss of dopaminergic neurons ( 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

• 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

neuronal intranuclear inclusions ( J:119515 )

muscle

muscle spasm ( J:119515 )

• twitching is observed at 20 weeks of age

homeostasis/metabolism

decreased dopamine level ( J:119515 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:119515

Allelic Composition	Tfam^tm1Lrsn/Tfam^tm1Lrsn 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:
Tfam^tm1Lrsn mutation (1 available); any Tfam mutation (14 available)
Tg(Myhca-cre)1Lrsn mutation (0 available)

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

mortality/aging

premature death ( J:61372 )

• animals surviving past neonatal stage survive for several months; variable penetrance speculated to be the result of a modifying gene

neonatal lethality, incomplete penetrance ( J:61372 )

• 75% of animals die as neonates

cardiovascular system

dilated heart atrium ( J:61372 )

increased heart weight ( J:61372 )

dilated heart left ventricle ( J:61372 )

dilated heart right ventricle ( J:61372 )

cellular

abnormal respiratory electron transport chain ( J:61372 )

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

growth/size/body

increased heart weight ( J:61372 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Kearns-Sayre syndrome		DOID:12934	OMIM:530000	J:61372

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