Phenotypes associated with this allele

• Allele Symbol: Ei24^tm1Hzha
• Allele Name: targeted mutation 1, Hong Zhang
• Allele ID: MGI:5475023
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ei24^tm1Hzha/Ei24^tm1Hzha Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:5475096
cn2	Ei24^tm1Hzha/Ei24^tm1Hzha Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5475097

Genotype
MGI:5475096

cn1

• Allelic Composition: Ei24^tm1Hzha/Ei24^tm1Hzha; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

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

Hepatomegaly and tumor-like protrusions in the liver of Ei24^tm1Hzha/Ei24^tm1Hzha Speer6-ps1^{Tg(Alb-cre)21Mgn}/0 mice

homeostasis/metabolism

impaired autophagy ( J:193420 )

• impaired autophagic flux in the liver at 3 months

liver/biliary system

abnormal liver morphology ( J:193420 )

• by 10 months, livers exhibit multiple tumor-like protusions with no signs of malignancy

enlarged liver ( J:193420 )

• by 3 months

abnormal liver lobule morphology ( J:193420 )

• disorganized hepatic lobules

abnormal hepatocyte morphology ( J:193420 )

• swollen hepatocytes with swollen mitochondria

abnormal hepatocyte mitochondrial morphology ( J:193420 )

• swollen

growth/size/body

enlarged liver ( J:193420 )

• by 3 months

cellular

abnormal hepatocyte mitochondrial morphology ( J:193420 )

• swollen

impaired autophagy ( J:193420 )

• impaired autophagic flux in the liver at 3 months

Genotype
MGI:5475097

cn2

• Allelic Composition: Ei24^tm1Hzha/Ei24^tm1Hzha; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Limb-clasping in Ei24^tm1Hzha/Ei24^tm1Hzha Tg(Nes-cre)1Kln/0 mice

homeostasis/metabolism

impaired autophagy ( J:193420 )

• impaired autophagic flux in the brain and spinal cord at 4 months

mortality/aging

premature death ( J:193420 )

• 50% of mice die by 16 weeks

• all mice die by 19 weeks

nervous system

nervous system phenotype ( J:196603 )

N • mice do not exhibit accumulation of TDP-43 (Tardbp) aggregates in motor neurons

increased neuron apoptosis ( J:193420 )

• massive

abnormal nervous system morphology ( J:193420 )

• neural abnormalities increase progressively with age

astrocytosis ( J:193420 )

• in the cerebrum, cerebellum and spinal cord

abnormal oligodendrocyte morphology ( J:193420 )

• numerous vacuolated cells in the spinal cord gray and white matter

reduced cerebellar foliation ( J:193420 )

enlarged lateral ventricles ( J:193420 )

abnormal brain white matter morphology ( J:193420 )

• thin white matter between the cortex and hippocampal pyramidal cells

abnormal hippocampus pyramidal cell layer ( J:193420 )

• thin

abnormal cerebral cortex morphology ( J:193420 )

• atrophic

thin cerebral cortex ( J:193420 )

• reduced ratio of cortical to dorsoventral thickness

abnormal Purkinje cell morphology ( J:193420 )

• shrunken appearance

decreased Purkinje cell number ( J:193420 )

• with age

thin cerebellar molecular layer ( J:193420 )

abnormal cerebellum fissure morphology ( J:193420 )

• reduced

brain vacuoles ( J:193420 )

• vacuolated cells in the cingulate cortex and to a lesser extent in other cortices, hippocampus, thalamus, and hypothalamus

• vacuolated cells in the white matter regions including the corpus callosum, the alveus of the hippocampus and the internal capsule

abnormal axon morphology ( J:193420 )

• irregularly arranged in the alveus of the hippocampus

decreased myelin sheath thickness ( J:193420 )

• thinned and split in the deep cerebellar nuclei axons

decreased neuron number ( J:193420 )

• in cortical layers 1 through 4

• reduced interneuron numbers in the anterior horn of the lumbar spinal cord

• however, the number of motor neurons is normal

decreased hippocampus pyramidal cell number ( J:193420 )

decreased cerebral cortex pyramidal cell number ( J:193420 )

• in the fifth layers of the motor and sensory cortices

neuronal cytoplasmic inclusions ( J:193420 )

• in the cerebrum, cerebellum and spinal cord that increase in number and size with age

axon degeneration ( J:193420 )

• massive

• of Purkinje cell axons

axonal dystrophy ( J:193420 )

• of Purkinje cell axon terminals

axonal spheroids ( J:193420 )

• eosinophilic spheroids in the cortex

• large eosinophilic spheroids in the deep cerebellar nuclei

behavior/neurological

abnormal behavior ( J:193420 )

• motor and behavioral deficits beginning at 6 weeks and progressively worsening

abnormal motor capabilities/coordination/movement ( J:193420 )

• beginning at 6 weeks and progressively worsening

abnormal involuntary movement ( J:193420 )

• hyperextended position of hind limbs

limb grasping ( J:193420 )

• in 8 of 12 mice at 6 weeks

• in all mice at 8 weeks

tremors ( J:193420 )

• at 8 weeks

ataxia ( J:193420 )

• at 12 weeks

impaired coordination ( J:193420 )

• at 3 months

growth/size/body

decreased body weight ( J:193420 )

• by 3 months

postnatal growth retardation ( J:193420 )

• at 2 weeks

cellular

astrocytosis ( J:193420 )

• in the cerebrum, cerebellum and spinal cord

abnormal oligodendrocyte morphology ( J:193420 )

• numerous vacuolated cells in the spinal cord gray and white matter

impaired autophagy ( J:193420 )

• impaired autophagic flux in the brain and spinal cord at 4 months

increased neuron apoptosis ( J:193420 )

• massive