Phenotypes associated with this allele

• Allele Symbol: Psmf1^{tm1c(EUCOMM)Hmgu}
• Allele Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
• Allele ID: MGI:6835662
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Psmf1^tm1c(EUCOMM)Hmgu/Psmf1^tm1c(EUCOMM)Hmgu Mnx1^tm4(cre)Tmj/Mnx1^+	involves: 129S1/Sv * C57BL/6J * C57BL/6N	MGI:6838401
cn2	Psmf1^tm1c(EUCOMM)Hmgu/Psmf1^tm1c(EUCOMM)Hmgu Tg(Pcp2-cre)GN135Gsat/0	involves: C57BL/6J * C57BL/6N * FVB/N	MGI:6838409
cn3	Psmf1^tm1c(EUCOMM)Hmgu/Psmf1^tm1c(EUCOMM)Hmgu Tg(CDX2-cre)101Erf/0	involves: C57BL/6J * C57BL/6N * SJL/J	MGI:6838400

Genotype
MGI:6838401

cn1

• Allelic Composition: Psmf1^{tm1c(EUCOMM)Hmgu}/Psmf1^{tm1c(EUCOMM)Hmgu}; Mnx1^tm4(cre)Tmj/Mnx1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J * C57BL/6N

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

growth/size/body

decreased body weight ( J:282431 )

• 5-month-old mice show a reduction in body weight

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:282431 )

• mice develop motor defects by 5 months of age that become progressively more severe with age

• overt motoric defects recapitulate phenotypes for amyotrophic lateral sclerosis (ALS 3A)

nervous system

abnormal axon morphology ( J:282431 )

• swelling of axonal tips in motor neurons is apparent as early as 1 month after birth and becomes progressively more severe with age

abnormal neuromuscular synapse morphology ( J:282431 )

• mice show severe structural abnormalities of the neuromuscular junction (NMJ), including presynaptic fragmentation of the NMJ, axonal tip swellings, and massive axonal sprouting that are notable at 5 months of age

axon degeneration ( J:282431 )

muscle

muscular atrophy ( J:282431 )

• mice develop muscle atrophy by 5 months of age that becomes progressively more severe with age

• 5-month-old mice show highly atrophied thoracic musculature

skeleton

kyphosis ( J:282431 )

• mice develop kyphosis of the spine by 5 months of age that becomes progressively more severe with age

• severe kyphosis is due to atrophy and weakness of paraspinal muscles

Genotype
MGI:6838409

cn2

• Allelic Composition: Psmf1^{tm1c(EUCOMM)Hmgu}/Psmf1^{tm1c(EUCOMM)Hmgu}; Tg(Pcp2-cre)GN135Gsat/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/N

behavior/neurological

impaired balance ( J:282431 )

• by P60, mice have severely disrupted balance, frequently drag their bodies along the ledge and fall on their heads when lowering themselves into the cage

abnormal locomotor behavior ( J:282431 )

• older mice exhibit locomotor defects

abnormal gait ( J:282431 )

• mice exhibit an aberrant halting gait and frequently lose their balance by P30 (but not a P21) in the ledge test and gait analysis

hematopoietic system

microgliosis ( J:282431 )

• reactive microglia become detectable in the deep cerebellar nuclei at P22 and gliosis becomes more severe at P30

immune system

microgliosis ( J:282431 )

• reactive microglia become detectable in the deep cerebellar nuclei at P22 and gliosis becomes more severe at P30

nervous system

microgliosis ( J:282431 )

• reactive microglia become detectable in the deep cerebellar nuclei at P22 and gliosis becomes more severe at P30

Purkinje cell degeneration ( J:282431 )

• a major reduction in Purkinje cell number is seen at 10 months of age

abnormal Purkinje cell dendrite morphology ( J:282431 )

• by P30, Purkinje cell primary and secondary dendrites appear swollen

abnormal cerebellum deep nucleus morphology ( J:282431 )

• by P60, the deep cerebellar nuclei contains large aggregates throughout which are positive for both poly-Ub conjugates and p62

astrocytosis ( J:282431 )

• by P30, a dramatic increase in reactive astrocytes is seen in the DCN, but not the Purkinje or molecular layers

• by P50, some reactive astrocytes are seen in the Purkinje layer

abnormal axon morphology ( J:282431 )

• swellings along the length of the axons in the white matter

abnormal Purkinje cell axon morphology ( J:282431 )

• Purkinje cell axon terminals in the deep cerebellar nuclei have swellings

• Purkinje cells lose almost all of their axon terminals in the deep cerebellar nuclei by 10 months of age

abnormal Purkinje cell focal axonal swelling ( J:282431 )

• axonal torpedoes, focal swellings on Purkinje cell axons are seen by 10 months of age

abnormal synaptic bouton morphology ( J:282431 )

• progressive damage to Purkinje cell axon terminals

Genotype
MGI:6838400

cn3

• Allelic Composition: Psmf1^{tm1c(EUCOMM)Hmgu}/Psmf1^{tm1c(EUCOMM)Hmgu}; Tg(CDX2-cre)101Erf/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * SJL/J

mortality/aging

postnatal lethality, complete penetrance ( J:282431 )

• all mice die by 3 to 4 weeks of age

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:282431 )

• mice begin to develop progressive neuromotor phenotypes around P6, characterized by spasticity, rigid muscle tone, strong tremor, and severely impaired righting response

impaired righting response ( J:282431 )

• severely impaired righting response

limb grasping ( J:282431 )

• mice exhibit hindlimb clasping between episodes of tremor when picked up by tails

tremors ( J:282431 )

• strong tremor

hindlimb paralysis ( J:282431 )

• mice are only able to move using their front legs since their hind limbs are hyperextended and paralyzed

spasticity ( J:282431 )

muscle

abnormal muscle tone ( J:282431 )

• rigid muscle tone