Phenotypes associated with this allele

• Allele Symbol: Tardbp⁺
• Allele Name: wild type
• Allele ID: MGI:2445358
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Tardbp^Gt(RRB030)Byg/Tardbp^+	B6.129P2-Tardbp^Gt(RRB030)Byg	MGI:4442984
ht2	Tardbp^tm1.1Neas/Tardbp^+	B6(C3)-Tardbp^tm1.1Neas	MGI:6405399
ht3	Tardbp^tm2.1Neas/Tardbp^+	B6(C3)-Tardbp^tm2.1Neas	MGI:6405402
ht4	Tardbp^em1Rhbr/Tardbp^+	C57BL/6J-Tardbp^em1Rhbr	MGI:6187718
ht5	Tardbp^tm1b(EUCOMM)Wtsi/Tardbp^+	C57BL/6N-Tardbp^tm1b(EUCOMM)Wtsi/H	MGI:5797852
ht6	Tardbp^m1H/Tardbp^+	involves: C3H/HeH * C57BL/6J	MGI:5575773
ht7	Tardbp^tm3.1Ckjs/Tardbp^+	involves: C57BL/6J	MGI:6404636
ht8	Tardbp^tm1.1Hiok/Tardbp^+	involves: C57BL/6J	MGI:7284280
ht9	Tardbp^tm2(TARDBP*A382T/Venus)Okn/Tardbp^+	Not Specified	MGI:5819110
ht10	Tardbp^tm1(TARDBP*G348C/Venus)Okn/Tardbp^+	Not Specified	MGI:5819109
cn11	Tardbp^tm1.1Pcw/Tardbp^+ Tg(CAG-cre/Esr1*)5Amc/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:4834589
cn12	Gt(ROSA)26Sor^tm1(cre/ERT)Nat/Gt(ROSA)26Sor^+ Tardbp^tm1.1Pcw/Tardbp^+	involves: 129 * C57BL/6 * SJL	MGI:4834588
cx13	Tardbp^m1H/Tardbp^+ Tg(SOD1*G93A)^dl1Gur/0	involves: C3H/HeH * C57BL/6 * C57BL/6J * SJL	MGI:5575774
cx14	Tardbp^tm3.1Ckjs/Tardbp^+ Tg(Hlxb9-GFP)1Tmj/0	involves: C57BL/6 * C57BL/6J * CBA	MGI:6404639

Genotype
MGI:4442984

ht1

• Allelic Composition: Tardbp^{Gt(RRB030)Byg}/Tardbp⁺
• Genetic Background: B6.129P2-Tardbp^{Gt(RRB030)Byg}

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

behavior/neurological

decreased grip strength ( J:158641 )

• as measured by hang time on an inverted grid and digital force gage in aged mice (536 - 581 days of age) but not in young mice (30 days of age)

Genotype
MGI:6405399

ht2

• Allelic Composition: Tardbp^tm1.1Neas/Tardbp⁺
• Genetic Background: B6(C3)-Tardbp^tm1.1Neas

nervous system

nervous system phenotype ( J:283769 )

N • mice show normal number of motor neurons in the lumbar levels, no motor neuron degeneration at 2 years of age, no denervation of the tibialis anterior muscle endplate and, no TDP-43-positive neuronal cytoplasmic inclusions

Genotype
MGI:6405402

ht3

• Allelic Composition: Tardbp^tm2.1Neas/Tardbp⁺
• Genetic Background: B6(C3)-Tardbp^tm2.1Neas

nervous system

nervous system phenotype ( J:283769 )

N • mice show normal number of motor neurons in the lumbar levels, no motor neuron degeneration at 2 years of age, no denervation of the tibialis anterior muscle endplate and, no TDP-43-positive neuronal cytoplasmic inclusions

Genotype
MGI:6187718

ht4

• Allelic Composition: Tardbp^em1Rhbr/Tardbp⁺
• Genetic Background: C57BL/6J-Tardbp^em1Rhbr

behavior/neurological

abnormal learning/memory/conditioning ( J:261673 )

♂ • learning deficits observed by 12 months of age

♂ • inattention phenotype reflecting frontal or executive dysfunction

abnormal object recognition memory ( J:261673 )

♂ • deficit in choice phase of spontaneous object recognition task

impaired coordination ( J:261673 )

♂ • reduced rotarod latency is observed in a 6 month old cohort

decreased stereotypic behavior ( J:261673 )

♂ • marble burying (innate digging) behavior is decreased in some mutants, however, other mutants perform similar to wild-type

Genotype
MGI:5797852

ht5

• Allelic Composition: Tardbp^{tm1b(EUCOMM)Wtsi}/Tardbp⁺
• Genetic Background: C57BL/6N-Tardbp^{tm1b(EUCOMM)Wtsi}/H
• Cell Lines: EPD0828_4_C03

Data Sources

IMPC Data for Tardbp

behavior/neurological

abnormal startle reflex ( J:211773 )

♂

IMPC - HAR

hematopoietic system

decreased mean platelet volume ( J:211773 )

♀

IMPC - HAR

homeostasis/metabolism

decreased blood urea nitrogen level ( J:211773 )

♀

IMPC - HAR

skeleton

decreased bone mineral content ( J:211773 )

♂

IMPC - HAR

decreased bone mineral density ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:5575773

ht6

• Allelic Composition: Tardbp^m1H/Tardbp⁺
• Genetic Background: involves: C3H/HeH * C57BL/6J

muscle

impaired muscle relaxation ( J:211620 )

• in the extensor digitorum longus

abnormal muscle tone ( J:211620 )

• soft abdominal body tone in male and female mice

behavior/neurological

limb grasping ( J:211620 )

♀ • in female at 61 weeks

♀ • however, male mice did not exhibit this phenotype but were not assessed beyond 52 weeks of age

nervous system

nervous system phenotype ( J:211620 )

N • mice exhibit normal neuromuscular junctions in the abdomen and hindlimbs

Genotype
MGI:6404636

ht7

• Allelic Composition: Tardbp^tm3.1Ckjs/Tardbp⁺
• Genetic Background: involves: C57BL/6J

mortality/aging

premature death ( J:285792 )

• males show a shorter life span, with an average of 19.5 +/- 2 months

• survival of females is longer than males, with average age being 25.5 +/- 6 months

• male-to-female ratio of the surviving pups is 1 to 2.6

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:285792 )

• males exhibit motor dysfunction at 6 months of age or older

• however, young and old males do not show impaired performance on the T-maze task

• disease onset in females is highly variable and about 30% of females are indistinguishable from wild-type females

limb grasping ( J:285792 )

♂ • males start to show hind limb-clasping around 8 months of age

tremors ( J:285792 )

♂ • mice exhibit spastic and trembled gait at 18 months and beyond

impaired coordination ( J:285792 )

♂ • males show a shorter latency to fall than wild-type mice starting after 5 months of age

hindlimb paralysis ( J:285792 )

♂ • males develop hindlimb paralysis with age

spasticity ( J:285792 )

♂ • mice exhibit spastic and trembled gait at 18 months and beyond

growth/size/body

weight loss ( J:285792 )

♂ • males lose weight after 18 months of age

muscle

skeletal muscle atrophy ( J:285792 )

♂ • 12 and 24 month old males exhibit skeletal muscle atrophy, with a decrease in wet weight of soleus muscle and reduction of calf muscle volume

nervous system

astrocytosis ( J:285792 )

♂ • astrogliosis is seen in the spinal cord in aged, but not 6 month, mice

abnormal motor neuron morphology ( J:285792 )

♂ • the level of ubiquitinated proteins is increased in the ChAT+ motor neurons of spinal cord of 6 month or older males, most of which are in the cytosol

motor neuron degeneration ( J:285792 )

♂ • males show an age-dependent loss of spinal cord motor neurons, with nearly 30%, 62%, and 77% loss at 6 months, 12 months, and 24 months, respectively

♂ • 30% loss of motor neurons in the lumbar region of the spinal cord at 6 months of age while the motor cortex, especially the primary motor cortex, only shows NeuN+ neuron loss at 24 months of age, indicating that lower motor neurons are affected first and then pathology spreads to the upper motor neurons

♂ • however, males do not show loss of neurons in the dentate gyrus, CA1 or CA3 regions of hippocampus

abnormal neuromuscular synapse morphology ( J:285792 )

♂ • 6 month old males show denervation of the neuromuscular junction of soleus muscle which progresses with ageing

neuronal cytoplasmic inclusions ( J:285792 )

♂ • TDP-43+ aggregates appear in the cytosol of spinal cord motor neurons of 12 and 24 month old males and colocalize with ubiquitinated proteins

skeleton

kyphosis ( J:285792 )

♂ • males start to show kyphosis at around 8 months of age

cellular

astrocytosis ( J:285792 )

♂ • astrogliosis is seen in the spinal cord in aged, but not 6 month, mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:285792

Genotype
MGI:7284280

ht8

• Allelic Composition: Tardbp^tm1.1Hiok/Tardbp⁺
• Genetic Background: involves: C57BL/6J

nervous system

abnormal cerebral cortex morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in frontal association cortex and M2 motor cortex from age 12 months

abnormal frontal lobe morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in frontal association cortex from age 12 months

abnormal primary motor cortex morphology ( J:308471 )

• early-stage transcriptional repression-induced atypical cell death (TRIAD) necrosis of neurons in cerebral cortex from ages 1 to 12 months, peaking at 3 months

behavior/neurological

impaired spatial learning ( J:308471 )

• increased latency to find platform in Morris water maze test from age 6 months

increased anxiety-related response ( J:308471 )

• increased distance traveled in open field test and less time spent in light in light-dark box test from age 6 months

cellular

abnormal endoplasmic reticulum morphology ( J:308471 )

• ER expansion in cortical neurons

abnormal cell cycle checkpoint function ( J:308471 )

• delayed or arrested G1/S transition in embryonic neural stem cells (NSCs) from cerebral cortex of E15 embryos

growth/size/body

increased body weight ( J:308471 )

• heavier by age 18 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255		J:308471

Genotype
MGI:5819110

ht9

• Allelic Composition: Tardbp^{tm2(TARDBP*A382T/Venus)Okn}/Tardbp⁺
• Genetic Background: Not Specified

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:231836 )

• gradual adult-onset motor dysfunction from 7 months of age

growth/size/body

slow postnatal weight gain ( J:231836 )

• poor weight gain

Genotype
MGI:5819109

ht10

• Allelic Composition: Tardbp^{tm1(TARDBP*G348C/Venus)Okn}/Tardbp⁺
• Genetic Background: Not Specified

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:231836 )

• gradual adult-onset motor dysfunction from 7 months of age

growth/size/body

slow postnatal weight gain ( J:231836 )

• poor weight gain

Genotype
MGI:4834589

cn11

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

growth/size/body

decreased body weight ( J:164406 )

• after cre induction by tamoxifen, mice show decrease in body weight relative to controls

adipose tissue

abnormal brown fat cell morphology ( J:164406 )

• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected

abnormal white fat cell morphology ( J:164406 )

• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected

Genotype
MGI:4834588

cn12

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺; Tardbp^tm1.1Pcw/Tardbp⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

growth/size/body

decreased body weight ( J:164406 )

• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not

homeostasis/metabolism

abnormal respiratory quotient ( J:164406 )

• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6

adipose tissue

decreased total body fat amount ( J:164406 )

• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice

• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass

Genotype
MGI:5575774

cx13

• Allelic Composition: Tardbp^m1H/Tardbp⁺; Tg(SOD1*G93A)^dl1Gur/0
• Genetic Background: involves: C3H/HeH * C57BL/6 * C57BL/6J * SJL

mortality/aging

premature death ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

muscle

decreased extensor digitorum longus weight ( J:211620 )

• compared with Tg(SOD1*G93A)1Gur mice

impaired muscle relaxation ( J:211620 )

• however, relaxation time in the extensor digitorum longus is normal

• in the tibialis anterior compared with Tg(SOD1*G93A)1Gur mice

abnormal muscle tone ( J:211620 )

• soft abdominal body tone as in Tardbp^m1H heterozygotes

behavior/neurological

decreased grip strength ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

growth/size/body

decreased body weight ( J:211620 )

• as in Tg(SOD1*G93A)1Gur mice

nervous system

nervous system phenotype ( J:211620 )

N • mice exhibit normal numbers of motor neurons in the sciatic motor pool

limbs/digits/tail

decreased extensor digitorum longus weight ( J:211620 )

• compared with Tg(SOD1*G93A)1Gur mice

Genotype
MGI:6404639

cx14

• Allelic Composition: Tardbp^tm3.1Ckjs/Tardbp⁺; Tg(Hlxb9-GFP)1Tmj/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:285792 )

• embryonic stem cell-derived spinal motor neurons show increased cytosolic calcium ion concentrations

nervous system

abnormal motor neuron morphology ( J:285792 )

• embryonic stem cells differentiated to motor neurons in culture show a reduction in survival on day 14 in culture

abnormal axon morphology ( J:285792 )

• embryonic stem cells differentiated to motor neurons in culture show a reduction in average axon length on day 14 in culture