Phenotypes associated with this allele

• Allele Symbol: Madd^tm1Ytk
• Allele Name: targeted mutation 1, Yoshimi Takai
• Allele ID: MGI:3762127
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Madd^tm1Ytk/Madd^tm1Ytk	involves: 129X1/SvJ	MGI:3762138
hm2	Madd^tm1Ytk/Madd^tm1Ytk	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:3762131

Genotype
MGI:3762138

hm1

• Allelic Composition: Madd^tm1Ytk/Madd^tm1Ytk
• Genetic Background: involves: 129X1/SvJ

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

nervous system

abnormal synaptic vesicle morphology ( J:126302 )

• synaptic vesicle diameter of hippocampal neurons is reduced (40.7+/-0.8 nm compared to 50.8+/-0.7 nm in wild-type mice)

abnormal excitatory postsynaptic currents ( J:126302 )

• mice exhibit a reduced excitatory postsynaptic current (EPSC; 1135+/-1925 pA compared to 5111+/-596 pA in wild-type mice)

• the paired pulse modulation ratio is increased (1.53+/-0.08% compared to 0.96+/-0.02% in wild-type mice)

• increased extracellular calcium levels did not reduce the paired pulse modulation ratio as much as in wild-type mice

• mice exhibit a time-dependent change in the evoked EPSC amplitude from wild-type mice

biphasic excitatory postsynaptic current amplitude ( J:126302 )

• unlike in wild-type mice, the amplitude of evoked EPSC displays a biphasic profile with a peak before the declining phase and a steady-state phase

• however, the rising time EPSC is normal

abnormal miniature excitatory postsynaptic currents ( J:126302 )

• while the mean quantal size of miniature excitatory postsynaptic currents is similar to that in wild-type mice, the frequency of events is reduced (18.3+/-2.5 Hz compared to 34.3+/-4.4 Hz in wild-type mice)

Genotype
MGI:3762131

hm2

• Allelic Composition: Madd^tm1Ytk/Madd^tm1Ytk
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

neonatal lethality, complete penetrance ( J:126869 )

• mice die within 30 minutes of birth due to acute respiratory failure

nervous system

abnormal neuromuscular synapse morphology ( J:126869 )

• at E18.5, few (11.8+/-3.63% of numbers vesicles in wild-type mice) to no synaptic vesicles are detected in the neuromuscular junctions of the phrenic nerve and diaphragm

• structural abnormalities at the neuromuscular junctions include enlargement of the axon terminal, degeneration of the mitochondria, and large synaptic vesicles with no content

• unlike in wild-type mice, synaptic vesicles are docked away from the presynaptic plasma membrane

• however, postsynaptic vesicles and development and maturation of the peripheral nervous system is normal are normal

abnormal synaptic vesicle morphology ( J:126869 )

• unlike in wild-type mice, synaptic vesicles are docked away from the presynaptic plasma membrane

• however, postsynaptic vesicles and development and maturation of the peripheral nervous system are normal

abnormal synaptic vesicle number ( J:126869 )

• at E18.5, few (11.8+/-3.63% of numbers vesicles in wild-type mice) to no synaptic vesicles are detected in the neuromuscular junctions of the phrenic nerve and diaphragm

impaired ability to fire action potentials ( J:126869 )

• at E18.5, mice show no response to mild (30 V) and moderate (50 V) stimuli and only low grade spikes are produced by maximal intensity (98 V) given at the spinal cord or sciatic nerve

• at E18.5, mice exhibit response to stimuli at the diaphragm to the phrenic nerve

• however, nerve conduction in the spinal cord and phrenic nerve is normal as is reaction levels of acetylcholine receptors

respiratory system

primary atelectasis ( J:126869 )

• pulmonary tract fails to dilate at birth

respiratory failure ( J:126869 )

• mice die within 30 minutes of birth due to acute respiratory failure

behavior/neurological

hyporesponsive to tactile stimuli ( J:126869 )

• at birth mice display few responses to tactile stimuli