Phenotypes associated with this allele

• Allele Symbol: Unc13a^tm2Bros
• Allele Name: targeted mutation 2, Nils Brose
• Allele ID: MGI:3051217
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Unc13a^tm2Bros/Unc13a^tm2Bros	involves: FVB/N	MGI:3718445
hm2	Unc13a^tm2Bros/Unc13a^tm2Bros	Not Specified	MGI:3718431
ht3	Unc13a^tm2Bros/Unc13a^+	Not Specified	MGI:3718440
cx4	Unc13a^tm2Bros/Unc13a^+ Unc13b^tm2Bros/Unc13b^tm2Bros	Not Specified	MGI:3718430
cx5	Unc13a^tm2Bros/Unc13a^tm2Bros Unc13b^tm2Bros/Unc13b^tm2Bros	Not Specified	MGI:3718432

Genotype
MGI:3718445

hm1

• Allelic Composition: Unc13a^tm2Bros/Unc13a^tm2Bros
• Genetic Background: involves: FVB/N

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

mortality/aging

neonatal lethality, complete penetrance ( J:74347 )

• despite initially breathing, responding to tactile stimuli and exhibiting pain-avoidance reflexes, mice die within 1 to 2 hours of birth

nervous system

abnormal synaptic vesicle morphology ( J:74347 )

• probability of vesicle release is increased (10.5%+/-0.8% compared to 6.9%+/-0.6% in wild-type cells)

abnormal synaptic vesicle number ( J:74347 )

• ready releasable pools (RRPs) of vesicles are reduced

• however, the rate of RRP refill after complete depletion is normal

abnormal synaptic vesicle recycling ( J:74347 )

• after a 40Hz train, the recovery response to RRP depletion is slower than in wild-type cells

• after a 10Hz continuous stimulation in a hypertonic solution and return to normal osmolarity, the recovery response to RRP depletion is slower than in wild-type cells

abnormal excitatory postsynaptic currents ( J:74347 )

• while excitatory postsynaptic currents are normal they only exhibit a small response to treatment with (4beta-phorbol-12,13-dibutyrate) PDBu

• at 10Hz action potential trains, excitatory postsynaptic current depression is enhanced relative to that in wild-type cells

Genotype
MGI:3718431

hm2

• Allelic Composition: Unc13a^tm2Bros/Unc13a^tm2Bros
• Genetic Background: Not Specified

mortality/aging

neonatal lethality, complete penetrance ( J:117827 )

• mice die within 1 to 2 hours of birth

Genotype
MGI:3718440

ht3

• Allelic Composition: Unc13a^tm2Bros/Unc13a⁺
• Genetic Background: Not Specified

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:108689 )

N • mice have normal glucose tolerance

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:108689 )

• mice exhibit a reduction in the size of ready releasable pools (RRPs) of vesicles in islet cells and do not respond to PMA (12-myristate 13-acetate ester) treatment

Genotype
MGI:3718430

cx4

• Allelic Composition: Unc13a^tm2Bros/Unc13a⁺; Unc13b^tm2Bros/Unc13b^tm2Bros
• Genetic Background: Not Specified

nervous system

abnormal synaptic vesicle morphology ( J:117827 )

• spontaneous release rates are intermediate and are increased by PDBu (4beta-phorbol-12,13-dibutyrate) treatment

abnormal synaptic vesicle number ( J:117827 )

• the number of fusion-competent vesicles is reduced to 2763+/-305 vesicles compared to 4109+/-722 vesicles in wild-type mice

abnormal excitatory postsynaptic currents ( J:117827 )

• at 10Hz action potential trains, excitatory postsynaptic current depression is enhanced relative to that in wild-type cells but not as much as in homozygotes and further enhanced by treatment with PDBu (4beta-phorbol-12,13-dibutyrate)

Genotype
MGI:3718432

cx5

• Allelic Composition: Unc13a^tm2Bros/Unc13a^tm2Bros; Unc13b^tm2Bros/Unc13b^tm2Bros
• Genetic Background: Not Specified

nervous system

abnormal synaptic vesicle morphology ( J:117827 )

• the rate of vesicle release is doubled compared to in wild-type cells for all doses tested

• spontaneous release rates are increased and are not effected by PDBu (4beta-phorbol-12,13-dibutyrate) treatment

• the probability of vesicle release is increased relative to in wild-type cells

abnormal synaptic vesicle number ( J:117827 )

• the number of fusion-competent vesicles is reduced to 2299+/-300 vesicles compared to 4109+/-722 vesicles in wild-type mice

• following stimulation with 250mM sucrose, the number of vesicles released is greater (2000+/-460 vesicles) than in wild-type cells (1100+/-300 vesicles)

abnormal excitatory postsynaptic currents ( J:117827 )

• at 10Hz action potential trains, excitatory postsynaptic current depression is enhanced relative to that in wild-type cells and is further enhanced by treatment with PDBu by (4beta-phorbol-12,13-dibutyrate)

abnormal miniature excitatory postsynaptic currents ( J:117827 )

• the absolute frequency of miniature excitory postsynaptic currents is more than doubled that in wild-type cells but similar to that in phorbol ester-treated wild-type cells

abnormal long-term depression ( J:117827 )

• long term potential is enhanced relative to in wild-type cells but similar to in that in wild-type cells treated with PDBu (4beta-phorbol-12,13-dibutyrate)