Phenotypes associated with this allele

• Allele Symbol: Cacna1e^tm1.1Tsch
• Allele Name: targeted mutation 1.1, Toni Schneider
• Allele ID: MGI:3526823
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1e^tm1.1Tsch/Cacna1e^tm1.1Tsch	involves: BALB/cJ * C57BL/6	MGI:3717625
hm2	Cacna1e^tm1.1Tsch/Cacna1e^tm1.1Tsch	involves: C57BL/6	MGI:3527983

Genotype
MGI:3717625

hm1

• Allelic Composition: Cacna1e^tm1.1Tsch/Cacna1e^tm1.1Tsch
• Genetic Background: involves: BALB/cJ * C57BL/6

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

homeostasis/metabolism

decreased glucagon secretion ( J:101873 )

• following carbachol treatment, glucagons release is impaired

• in vitro, Langerhan's islets fail to suppress glucagons secretion following elevated glucose levels

decreased insulin secretion ( J:95636 )

• following glucose stimulation, insulin secretion is reduced

• following glucose stimulation, secretion from Langerhan's islets is reduced

increased circulating glucose level ( J:101873 )

• serum glucose levels are increased to 133+/-4 mg/dl compared to 123+/-3 mg/dl in wild-type mice

hyperglycemia ( J:95636 )

• younger mice exhibit an attenuated hyperglycemic stress response

impaired glucose tolerance ( J:95636 )

• at 10 weeks, glucose tolerance is impaired

• impaired glucose response is partially compensated with age

decreased physiological sensitivity to xenobiotic ( J:101873 )

• following carbachol treatment, glucagon release is impaired relative to controls

endocrine/exocrine glands

decreased glucagon secretion ( J:101873 )

• following carbachol treatment, glucagons release is impaired

• in vitro, Langerhan's islets fail to suppress glucagons secretion following elevated glucose levels

decreased insulin secretion ( J:95636 )

• following glucose stimulation, insulin secretion is reduced

• following glucose stimulation, secretion from Langerhan's islets is reduced

growth/size/body

increased body weight ( J:101873 )

• mice are slightly heavier weighing 29.7g+/-0.5g compared to wild-type mice that weigh 28.3g+/-0.4g

Genotype
MGI:3527983

hm2

• Allelic Composition: Cacna1e^tm1.1Tsch/Cacna1e^tm1.1Tsch
• Genetic Background: involves: C57BL/6

endocrine/exocrine glands

decreased pancreatic alpha cell number ( J:95377 )

• only 7% of dispersed islet cells were alpha cells in mutants compared to 27% of wild-type cells

abnormal glucagon secretion ( J:95377 )

• increased glucose levels did not suppress glucagon secretion as much in mutants as it did in wild-type islets, 27% reduction in mutants compared to a 58% reduction in wild-type islets

• an L-type channel antagonist stimulated glucagon release 52% in the presence of high glucose concentrations in wild-type islets but reduced glucagon secretion by 32% in mutant islets

abnormal pancreatic beta cell physiology ( J:95377 )

• at -10mV the integrated Ca²⁺ currents are reduced about 23% compared to wild-type; this reduction is limited to the high voltage Ca²⁺ current component

• the late component of exocytosis, but not the early component, is suppressed in mutant beta cells

decreased insulin secretion ( J:95377 )

• glucose stimulated insulin release is reduced about 25% in mutant islets compared to wild-type islets

• in situ pancreatic perfusion revealed that the initial peak of insulin secretion is normal however the second-phase of insulin release is reduced by about 46% compared to wild-type

homeostasis/metabolism

abnormal glucagon secretion ( J:95377 )

• increased glucose levels did not suppress glucagon secretion as much in mutants as it did in wild-type islets, 27% reduction in mutants compared to a 58% reduction in wild-type islets

• an L-type channel antagonist stimulated glucagon release 52% in the presence of high glucose concentrations in wild-type islets but reduced glucagon secretion by 32% in mutant islets

decreased insulin secretion ( J:95377 )

• glucose stimulated insulin release is reduced about 25% in mutant islets compared to wild-type islets

• in situ pancreatic perfusion revealed that the initial peak of insulin secretion is normal however the second-phase of insulin release is reduced by about 46% compared to wild-type

increased circulating glucose level ( J:95377 )

• basal glucose levels are elevated by 17% compared to wild-type mice

decreased circulating glucagon level ( J:95377 )

• basal glucagon levels are decreased about 10% compared to wild-type mice and after glucose challenge plasma glucagon levels are increased about 18% in contrast to wild-type mice where after a glucose challenge glucagon levels are decreased by 15%

impaired glucose tolerance ( J:95377 )

• 3 and 8 minutes after a glucose challenge plasma glucose levels are elevated about 15% in mutants compared to wild-type mice