Phenotypes associated with this allele

• Allele Symbol: Cadps^tm1Bros
• Allele Name: targeted mutation 1, Nils Brose
• Allele ID: MGI:3583931
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cadps^tm1Bros/Cadps^tm1Bros	Not Specified	MGI:3603016
ht2	Cadps^tm1Bros/Cadps^+	Not Specified	MGI:3603017
cx3	Cadps^tm1Bros/Cadps^tm1Bros Cadps2^tm1Bros/Cadps2^tm1Bros	Not Specified	MGI:3808793
cx4	Cadps^tm1Bros/Cadps^+ Cadps2^tm1Bros/Cadps2^tm1Bros	Not Specified	MGI:3808888

Genotype
MGI:3603016

hm1

• Allelic Composition: Cadps^tm1Bros/Cadps^tm1Bros
• Genetic Background: Not Specified

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

mortality/aging

neonatal lethality, complete penetrance ( J:99762 )

• homozygotes die within 10-30 min of birth

endocrine/exocrine glands

abnormal adrenal gland physiology ( J:99762 )

• dopamine levels are significantly decreased and levels of catecholamine degradation products are increased in the adrenals

abnormal adrenal gland secretion ( J:99762 )

• in adrenal slices from E19 homozygotes large dense-core vesicle secretion by chromaffin cells is decreased as a result of production of empty vesicles; however the number of vesicles that fuse to the membrane in response to stimulus and the number of vesicles adjacent to the membrane are similar to wild-type, unlike in 30 day old heterozygous mice

respiratory system

respiratory failure ( J:99762 )

• newborn homozygotes breath slowly at birth and further decrease breathing rates after birth; however lung morphology is normal

nervous system

nervous system phenotype ( J:99762 )

N • brain morphology, synaptic transmission in the autaptic hippocampal neurons, and hypoglossal nerve activity in the respiratory brainstem are all normal

abnormal neuron morphology ( J:131212 )

• size of pool of fusion competent and primed secretory vesicles (SVs) or readily releasable pool (RRP) of vesicles is reduced to 42% of wild-type

abnormal neuron physiology ( J:131212 )

• neurons which show no detectable EPSC fail to release neurotransmitter in response to hypertonic buffer

decreased excitatory postsynaptic current amplitude ( J:131212 )

• evoked EPSC amplitudes in autaptic cultures of hippocampal neurons are reduced to 51% of wild-type when a hypertonic sucrose solution is applied

• around 12% of neurons studied have no detectable evoked EPSCs

decreased miniature excitatory postsynaptic current amplitude ( J:131212 )

• mEPSC amplitude is reduced to 79% of control neurons

decreased miniature excitatory postsynaptic current frequency ( J:131212 )

• mEPSC requency is reduced to 40% of control neurons

Genotype
MGI:3603017

ht2

• Allelic Composition: Cadps^tm1Bros/Cadps⁺
• Genetic Background: Not Specified

endocrine/exocrine glands

abnormal adrenal gland secretion ( J:99762 )

• in adrenal slices from postnatal day 30 heterozygotes large dense-core vesicle secretion by chromaffin cells is decreased by about 70% compared to wild-type mice as a result of a decrease in the number of vesicles adjacent to the cell membrane

Genotype
MGI:3808793

cx3

• Allelic Composition: Cadps^tm1Bros/Cadps^tm1Bros; Cadps2^tm1Bros/Cadps2^tm1Bros
• Genetic Background: Not Specified

mortality/aging

neonatal lethality, complete penetrance ( J:131014 )

• mice die shortly after birth

nervous system

abnormal neuron morphology ( J:131212 )

• in autaptic cultures, in hippocampal neurons that do respond to stimulation with hypertonic buffer, pool size of fusion competent and primed secretory vesicles (SVs) or readily releasable pool (RRP) of vesicles is reduced to 42% of wild-type

• after trains of 10 Hz and 40 Hz stimuli, RRP size increases >3 fold and >5 fold respectively, whereas in control neurons, RRP is reduced to 56% and 64% of prestimulus values

• calcimycin induced release of synaptic vesicles is similar in extent to control neurons but release is delayed and slower

• abnormalities are not result of any major alteration in synapse morphology or number

abnormal neuron physiology ( J:131212 , J:167753 )

• in 39% of neurons tested no evoked EPSCs or neurotransmitter release is elicited in response to hypertonic buffer (J:131212)

• neuron are deficient in synaptic vesicle priming compared with control neurons (J:167753)

• calcium uncaging only induces slow release of synaptic vesicles compared to in control neurons (J:167753)

• slow flash induced discharge of synaptic vesicles is delayed compared to in control neurons (J:167753)

abnormal CNS synaptic transmission ( J:131212 )

• after high frequency stimulation, neurons can release neurotransmitter at wild-type levels soon after stimulation

abnormal excitatory postsynaptic current amplitude ( J:131212 )

• in neurons that do respond to stimulation with hypertonic buffer, EPSC amplitudes are reduced to 15% of control levels

• in response to trains of stimulation, EPSC amplitudes are increased 5 fold over baseline values, in contrast to control neurons which exhibit depressed EPSC amplitudes

• upon return to low stimulation frequency, EPSC amplitudes are augmented up to 6 fold such that EPSC amplitudes reach control values

abnormal miniature excitatory postsynaptic currents ( J:131212 )

• mEPSC amplitude and frequency are reduced to 77% and 23% respectively, of control neurons

• mEPSC frequency is increased 7.3 fold immediately after high frequency stimulation to prestimulus control levels

• EPSCs induced by calcimycin treatment facilitate transiently then depress gradually whereas EPSCs in control neurons depress rapidly

abnormal neurotransmitter secretion ( J:263391 )

• secretory defects in hippocampal neurons

endocrine/exocrine glands

abnormal adrenal gland secretion ( J:136362 , J:263391 )

• chromaffin cells from E18 and E19 embryos exhibit large deficit in catecholamine secretion; deficit is in priming of vesicles (J:136362)

• significant reduction in rapidly releasable pool (RRP) of large dense-core vesicles (LDVCs) in chromaffin cells is observed; a smaller (non-significant) reduction in the slowly releasing pool (SRP) of vesicles in response to flash photolysis whereas wild-type cells show RRP and SRP of similar burst amplitudes after the first and second flashes (J:136362)

• after flash photolysis stimulation with an interstimulus interval (ISI) of 45 seconds, the RRP is reduce and the SRP is modestly increased following the second flash; with an ISI of 25 seconds, RRP is markedly reduced and the SRP is overfilled whereas in wild-type, secretion is similar to that observed with a 45 second ISI (J:136362)

• with an ISI of 15 seconds, cells have almost no RRP and and significantly enhanced SRP (J:136362)

• calcium dependent secretion by wild-type chromaffin cells is 4 times greater than in double-null cells (J:136362)

• profound secretory deficits of chromaffin cells (J:263391)

Genotype
MGI:3808888

cx4

• Allelic Composition: Cadps^tm1Bros/Cadps⁺; Cadps2^tm1Bros/Cadps2^tm1Bros
• Genetic Background: Not Specified

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:131014 )

• insulin granule density is reduced by 25% compared to wild-type

• number of docked insulin granules is 44% lower than in wild-type cells

• cellular density of lysosomes is 60% higher than in wild-type cells

• rapidly releasable pool (RRP) of vesicles in beta cells in >50% lower than in wild-type

increased glucagon secretion ( J:131014 )

• secretion induced at 1mM glucose is increased significantly relative to wild-type but is inhibited by stimulation with 20 mM glucose

abnormal pancreatic beta cell physiology ( J:131014 )

• exocytosis in beta cells is impaired; basal exocytosis is reduced by >50%

• beta cell capacitance increase evoked by intracellular calcium ion dialyzation is reduced by 50% compared to wild-type cells

decreased insulin secretion ( J:131014 )

• basal (1mM glucose) and glucose-stimulated insulin secretion (GSIS; 20mM glucose) from pancreatic beta cells are reduced by 50-60% compared to wild-type cells

• insulin secretion evoked by potassium stimulation of beta cells is reduced by 50%

• insulin release from pancreatic islets at 10 minutes following glucose challenge is reduced by 55% compared to wild-type

homeostasis/metabolism

abnormal glucose homeostasis ( J:131014 )

increased glucagon secretion ( J:131014 )

• secretion induced at 1mM glucose is increased significantly relative to wild-type but is inhibited by stimulation with 20 mM glucose

decreased insulin secretion ( J:131014 )

• basal (1mM glucose) and glucose-stimulated insulin secretion (GSIS; 20mM glucose) from pancreatic beta cells are reduced by 50-60% compared to wild-type cells

• insulin secretion evoked by potassium stimulation of beta cells is reduced by 50%

• insulin release from pancreatic islets at 10 minutes following glucose challenge is reduced by 55% compared to wild-type

impaired glucose tolerance ( J:131014 )

• plasma glucose concentration is higher by 30% relative to wild-type at 45 minutes after glucose loading

increased insulin sensitivity ( J:131014 )

• enhanced compared to wild-type with larger decrease in plasma glucose following insulin injection

abnormal hormone level ( J:131014 )

• insulin content in pancreatic islets is reduced by 25% compared to wild-type islets

cellular

abnormal lysosome physiology ( J:131014 )

• lysosomal cathepsin D activity in lysosomes is 2.4 fold higher than in wild-type islets