Phenotypes associated with this allele

• Allele Symbol: Tardbp^tm1.1Ckjs
• Allele Name: targeted mutation 1.1, C K James Shen
• Allele ID: MGI:4418700
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tardbp^tm1.1Ckjs/Tardbp^tm1.1Ckjs	involves: C57BL/6J * FVB/N	MGI:4418702
cn2	Mnx1^tm4(cre)Tmj/Mnx1^+ Tardbp^tm1.1Ckjs/Tardbp^tm1.2Cjks	involves: 129S1/Sv * C57BL/6J	MGI:5513111

Genotype
MGI:4418702

hm1

• Allelic Composition: Tardbp^tm1.1Ckjs/Tardbp^tm1.1Ckjs
• Genetic Background: involves: C57BL/6J * FVB/N

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

Tardbp^tm1.1Ckjs/Tardbp^tm1.1Ckjs embryos show defective development of the inner cell mass in vitro

mortality/aging

embryonic lethality, complete penetrance ( J:155958 )

• embryonic lethal between E3.5 and E6.5

embryo

absent inner cell mass proliferation ( J:155958 )

• E3.5 embryos cultured for 3 days on adhered trophoblast giant cells fail to form the proliferative ICM

cellular

absent inner cell mass proliferation ( J:155958 )

• E3.5 embryos cultured for 3 days on adhered trophoblast giant cells fail to form the proliferative ICM

Genotype
MGI:5513111

cn2

• Allelic Composition: Mnx1^tm4(cre)Tmj/Mnx1⁺; Tardbp^tm1.1Ckjs/Tardbp^tm1.2Cjks
• Genetic Background: involves: 129S1/Sv * C57BL/6J

mortality/aging

premature death ( J:190254 )

• average lifespan of mutants showing amyotrophic lateral sclerosis-like phenotypes is 10 months

growth/size/body

decreased body weight ( J:190254 )

• average weight is slightly lower at early birth than in controls and this difference becomes more pronounced with age, with a significant weight difference after 8 weeks of age

weight loss ( J:190254 )

• while mutants show a peak of weight gain during 90-100 days of age, soon after this time, they begin to show weight loss

behavior/neurological

limb grasping ( J:190254 )

• abnormal hind limb clasping is seen after 13 weeks of age

impaired coordination ( J:190254 )

• mutants show a deficiency in the rotarod test after 13 weeks of age

immune system

increased microglial cell activation ( J:190254 )

• microglia activation is seen in the lateroventral lumbar spinal cord

muscle

muscular atrophy ( J:190254 )

• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1

muscle weakness ( J:190254 )

nervous system

increased microglial cell activation ( J:190254 )

• microglia activation is seen in the lateroventral lumbar spinal cord

astrocytosis ( J:190254 )

• in the spinal cord

abnormal motor neuron morphology ( J:190254 )

• accumulation of ubiquitinated proteins in the spinal cord motor neurons at 20 weeks of age

motor neuron degeneration ( J:190254 )

• progressive loss of motor neurons, with a 10% decrease of spinal cord motor neurons at 10 weeks of age and a large loss of ChAT-positive motor neurons at 20 weeks of age

• 46% and 25% reduction in alpha and gamma motor neurons, respectively, in the lumbar regions of the spinal cord at 20 weeks of age

• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1

abnormal spinal cord ventral horn morphology ( J:190254 )

• motor neuron loss, reactive astrocytosis, microglia activation and accumulation of polyubiquitinated proteins in the ventral horn

skeleton

kyphosis ( J:190254 )

• mutants exhibit kyphosis beginning at 20 weeks of age which becomes severe at 24 weeks

hematopoietic system

increased microglial cell activation ( J:190254 )

• microglia activation is seen in the lateroventral lumbar spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:190254