Phenotypes associated with this allele

• Allele Symbol: Unc13a^tm1Bros
• Allele Name: targeted mutation 1, Nils Brose
• Allele ID: MGI:2449468
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Unc13a^tm1Bros/Unc13a^tm1Bros	involves: 129	MGI:2654103
ht2	Unc13a^tm1Bros/Unc13a^+	involves: 129	MGI:3718441
cx3	Unc13a^tm1Bros/Unc13a^tm1Bros Unc13b^tm2Bros/Unc13b^tm2Bros	involves: 129	MGI:2654056
cx4	Stx1b^tm1.1Sud/Stx1b^tm1.1Sud Unc13a^tm1Bros/Unc13a^tm1Bros	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3832397

Genotype
MGI:2654103

hm1

• Allelic Composition: Unc13a^tm1Bros/Unc13a^tm1Bros
• Genetic Background: involves: 129

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

mortality/aging

neonatal lethality, complete penetrance ( J:56513 )

• mice die within a few hours of birth

postnatal lethality, complete penetrance ( J:138035 )

• no surviving offspring are found at P3

behavior/neurological

absent gastric milk in neonates ( J:138035 )

• newborn animals do not feed and stomachs do not display milk spots

weakness ( J:56513 )

• neonatal animals display weakness

nervous system

nervous system phenotype ( J:56513 )

N • normal brain cytoarchitecture and ultrastructure of CNS in newborn animals

abnormal synaptic vesicle number ( J:56513 )

• arrest of synaptic vesicle cycle maturation

decreased synaptic vesicle readily releasable pool size ( J:77339 )

• 90% reduction of readily releasable vesicles

abnormal CNS synaptic transmission ( J:138035 )

• excitatory postsynaptic responses induced by hypertonic sucrose application to cultured neurons are decreased compared to controls

• reduction in readily releasable pool of synaptic vesicles in excitatory synapses is observed in culture

decreased neurotransmitter release ( J:77339 )

• 90% reduction of readily releasable vesicles and evoked transmitter release

respiratory system

decreased pulmonary respiratory rate ( J:56513 )

• neonatal animals exhibit reduced breathing rate

cellular

abnormal synaptic vesicle number ( J:56513 )

• arrest of synaptic vesicle cycle maturation

decreased synaptic vesicle readily releasable pool size ( J:77339 )

• 90% reduction of readily releasable vesicles

Genotype
MGI:3718441

ht2

• Allelic Composition: Unc13a^tm1Bros/Unc13a⁺
• Genetic Background: involves: 129

homeostasis/metabolism

decreased insulin secretion ( J:108689 , J:215257 )

• in response to a glucose load, mice produce 52% less insulin compared to wild-type mice and 43% compared to Unc13a^tm2Bros hetrozygotes (J:108689)

• when stimulated PMA (12-myristate 13-acetate ester), with glucose-stimulated insulin secretion is reduced by 49.2% relative to wild-type mice (J:108689)

• however, fasting insulin levels are normal (J:108689)

• islet beta cells show reduced insulin exocytosis by about 50% when induced by a train of ten 500 ms depolarization pulses and decreased monoacylglycerol stimulation of exocytosis (J:215257)

impaired glucose tolerance ( J:108689 )

• in an intraperitoneal glucose tolerance test, mice are glucose intolerant

• with males exhibiting significantly higher glucose levels in response to a glucose load

• however, fasting glucose levels are normal

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:108689 )

• mice exhibit a reduction in the size of ready releasable pools of vesicles in islet cells but respond to PMA (12-myristate 13-acetate ester) treatment by increasing RRPs

decreased insulin secretion ( J:108689 , J:215257 )

• in response to a glucose load, mice produce 52% less insulin compared to wild-type mice and 43% compared to Unc13a^tm2Bros hetrozygotes (J:108689)

• when stimulated PMA (12-myristate 13-acetate ester), with glucose-stimulated insulin secretion is reduced by 49.2% relative to wild-type mice (J:108689)

• however, fasting insulin levels are normal (J:108689)

• islet beta cells show reduced insulin exocytosis by about 50% when induced by a train of ten 500 ms depolarization pulses and decreased monoacylglycerol stimulation of exocytosis (J:215257)

Genotype
MGI:2654056

cx3

• Allelic Composition: Unc13a^tm1Bros/Unc13a^tm1Bros; Unc13b^tm2Bros/Unc13b^tm2Bros
• Genetic Background: involves: 129

mortality/aging

neonatal lethality, complete penetrance ( J:77339 )

• all mutants born alive, die within 1 hour after birth

nervous system

abnormal synapse morphology ( J:77339 )

• length of active zones is larger in synapses, thus the number of docked vesicles per um active zone is lower, however mutants form normal numbers of synapses

• cultured neurons are unable to exocytose and lack calcium-triggered endocytotic activity

abnormal synaptic vesicle number ( J:77339 )

• complete loss of fusion competent vesicles

abnormal neuron physiology ( J:167753 )

• flash-response is abolished in neurons compared with control mice

abnormal synaptic transmission ( J:77339 )

• spontaneous, action potential evoked, and hypertonically evoked vesicular release (synaptic transmission) are abolished

abnormal excitatory postsynaptic currents ( J:167753 )

• excitatory postsynaptic current induced by calcium uncaging is abolished compared to in control mice

cellular

abnormal synaptic vesicle number ( J:77339 )

• complete loss of fusion competent vesicles

Genotype
MGI:3832397

cx4

• Allelic Composition: Stx1b^tm1.1Sud/Stx1b^tm1.1Sud; Unc13a^tm1Bros/Unc13a^tm1Bros
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

postnatal lethality ( J:138035 )

• homozygosity of the Stx1b mutant allele in combination with Unc13a-deficiency does not rescue the lethality observed for Unc13a-null mutants; no double homozygous mice are found at P3