Phenotypes associated with this allele

• Allele Symbol: Mapt^{tm3.1(FUS)Neas}
• Allele Name: targeted mutation 3.1, Neil A Shneider
• Allele ID: MGI:5776232
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mapt^tm3.1(FUS)Neas/Mapt^tm3.1(FUS)Neas	B6J.129P2(129S)-Mapt^tm3.1(FUS)Neas	MGI:5823862
ht2	Mapt^tm3.1(FUS)Neas/Mapt^+	B6J.129P2(129S)-Mapt^tm3.1(FUS)Neas	MGI:5823860
cn3	Fus^tm1a(EUCOMM)Wtsi/Fus^tm1c(EUCOMM)Wtsi Mapt^tm3.1(FUS)Neas/Mapt^+ Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129 * C3H * C57BL/6 * C57BL/6N	MGI:5824116

Genotype
MGI:5823862

hm1

• Allelic Composition: Mapt^{tm3.1(FUS)Neas}/Mapt^{tm3.1(FUS)Neas}
• Genetic Background: B6J.129P2(129S)-Mapt^{tm3.1(FUS)Neas}

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

nervous system

abnormal neuromuscular synapse morphology ( J:232167 )

• denervation of the tibialis anterior neuromuscular junctions

Genotype
MGI:5823860

ht2

• Allelic Composition: Mapt^{tm3.1(FUS)Neas}/Mapt⁺
• Genetic Background: B6J.129P2(129S)-Mapt^{tm3.1(FUS)Neas}

behavior/neurological

paraparesis ( J:232167 )

• hind-limb weakness; wire hang analysis of P360 mice shows that the average latency to fall is about half that of the controls

hematopoietic system

microgliosis ( J:232167 )

• motor neuron degeneration is associated with astrocytosis and microgliosis

immune system

microgliosis ( J:232167 )

• motor neuron degeneration is associated with astrocytosis and microgliosis

muscle

abnormal tibialis anterior morphology ( J:232167 )

• internal nuclei and decreased fiber diameter are seen in the tibialis anterior muscle

• sarcomere length in tibialis anterior muscle is reduced

abnormal sarcomere morphology ( J:232167 )

• sarcomere length in tibialis anterior muscle is reduced

nervous system

microgliosis ( J:232167 )

• motor neuron degeneration is associated with astrocytosis and microgliosis

astrocytosis ( J:232167 )

• motor neuron degeneration is associated with astrocytosis and microgliosis

abnormal motor neuron innervation pattern ( J:232167 )

• by P20, before motor neuron loss, 11.4% of neuromuscular junctions in the tibialis anterior have no associated input, indicating early retraction of motor axons

motor neuron degeneration ( J:232167 )

• loss of motor neurons at lumber level 5 (L5) is first seen at P30 and progresses steadily to P360

• however, no loss of parvalbumin-positive, proprioceptive sensory neurons in the L5 dorsal root ganglia is seen or of motor neuron loss in oculomotor nucleus at P360

• increase in spontaneous activity in motor neurons, a sign of active denervation of neurogenic origin

abnormal synaptic bouton morphology ( J:232167 )

• in the axon terminals of motor neurons, the number of morphologically normal mitochondria is decreased and the remaining mitochondria appear dilated and vacuolated with disorganized cristae and membranes

abnormal neuromuscular synapse morphology ( J:232167 )

• by P20, before motor neuron loss, 11.4% of neuromuscular junctions in the tibialis anterior have no associated input, indicating early retraction of motor axons

• denervation of the gastrocnemius muscle is seen at P90 when about 10% of neuromuscular junctions are vacant

• denervation in both the tibialis anterior and gastrocnemius muscles progresses steadily so that by P360, 36.7% and 19.3% of endplates are vacant in the respective muscles

• by P360, 36.7% and 19.3% of neuromuscular junctions are denervated in the tibialis anterior and gastrocnemius muscles, respectively

• by P360, only 10% of slow soleus muscle motor terminals are vacant

• at P30, neuromuscular junctions (NMJs) show pre-synaptic abnormalities, including a 40% reduction in the density of synaptic vesicles in the pre-synaptic terminals

• however, the number of active zones-the main apparatus for synaptic vesicle release-is unchanged

• in the axon terminals of motor neurons, the number of morphologically normal mitochondria is decreased and the remaining mitochondria appear dilated and vacuolated with disorganized cristae and membranes, while on the postsynaptic side of NMJs, abnormal mitochondria are seen

abnormal synaptic transmission ( J:232167 )

• at 50 Hz, a 45% reduction of the motor response amplitude in the tibialis anterior, suggesting that motor neurons cannot sustain reliable neurotransmission at the NMJs and exhibit abnormal synaptic depression

• at 100 Hz, mice exhibit synaptic depression, however the motor response in tibialis anterior motor neurons is often completely absent, indicating failure of neurotransmission

abnormal synaptic depression ( J:232167 )

• motor neurons exhibit abnormal synaptic depression

limbs/digits/tail

abnormal tibialis anterior morphology ( J:232167 )

• internal nuclei and decreased fiber diameter are seen in the tibialis anterior muscle

• sarcomere length in tibialis anterior muscle is reduced

Genotype
MGI:5824116

cn3

• Allelic Composition: Fus^{tm1a(EUCOMM)Wtsi}/Fus^{tm1c(EUCOMM)Wtsi}; Mapt^{tm3.1(FUS)Neas}/Mapt⁺; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129 * C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0667_5_C04

nervous system

abnormal neuromuscular synapse morphology ( J:232167 )

• mice treated with tamoxifen postnatally show denervation in the tibialis anterior muscle where about 12% of neuromuscular junctions are denervated