Phenotypes associated with this allele

• Allele Symbol: Abcc9^tm1Cfb
• Allele Name: targeted mutation 1, Charles F Burant
• Allele ID: MGI:2155916
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Abcc9^tm1Cfb/Abcc9^tm1Cfb	involves: CD-1	MGI:2653868
hm2	Abcc9^tm1Cfb/Abcc9^tm1Cfb	Not Specified	MGI:3622096

Genotype
MGI:2653868

hm1

• Allelic Composition: Abcc9^tm1Cfb/Abcc9^tm1Cfb
• Genetic Background: involves: CD-1

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

mortality/aging

premature death ( J:71840 )

• increased spontaneous death observed at 6 weeks of age in males and at 10 weeks of age in females

growth/size/body

slow postnatal weight gain ( J:71840 )

• weight gain begins to lag relative to that of wild-type mice after 6 weeks of age

homeostasis/metabolism

hypoglycemia ( J:71840 )

• at 10-12 weeks of age, fasted homozygotes show a small but significant reduction of serum glucose levels relative to wild-type mice

• however, no significant differences are noted in fasted serum electrolytes at 6-8 weeks of age or in fed or fasting serum insulin levels and fed or fasting serum triglyceride levels at 10-12 weeks of age relative to wild-type mice

improved glucose tolerance ( J:71840 )

• in response to i.p. injection of glucose (2 g/kg), homozygotes display a significantly improved glucose tolerance curve, with peak serum glucose levels of ~250 mg/dl at 30 min post-injection relative to 420 mg/dl in wild-type mice

• during in vivo hyperinsulinemic euglycemic clamp studies, homozygotes require a higher glucose infusion rate to maintain target serum glucose levels than wild-type mice

increased insulin sensitivity ( J:71840 )

• in response to 0.5 U/kg of insulin challenge, homozygotes exhibit a more rapid and sustained decrease in serum glucose than wild-type mice, with 50% of mutants either succumbing to hypoglycemia or requiring glucose injections to restore glucose levels

• increased insulin action is intrinsic to skeletal muscle, as shown by a 59% increase in in vitro insulin-stimulated glucose uptake into the soleus muscle

muscle

increased muscle cell glucose uptake ( J:71840 )

• following incubation with insulin, male homozygotes show a 1.5-fold increase in in vitro glucose uptake into skeletal (soleus) muscle relative to wild-type males

• however, in the absence of insulin, in vitro glucose uptake into mutant skeletal muscle is similar to that in wild-type, indicating normal basal glucose transport

cellular

increased muscle cell glucose uptake ( J:71840 )

• following incubation with insulin, male homozygotes show a 1.5-fold increase in in vitro glucose uptake into skeletal (soleus) muscle relative to wild-type males

• however, in the absence of insulin, in vitro glucose uptake into mutant skeletal muscle is similar to that in wild-type, indicating normal basal glucose transport

Genotype
MGI:3622096

hm2

• Allelic Composition: Abcc9^tm1Cfb/Abcc9^tm1Cfb
• Genetic Background: Not Specified

mortality/aging

premature death ( J:78066 )

• by 30 weeks of age, 65% of males and 35% of females die suddenly

cardiovascular system

artery stenosis ( J:78066 )

abnormal ST segment ( J:78066 )

• exhibit repeated episodes of spontaneous ST segment elevation that are often followed by slow heart rate, however show normal baseline resting heart rate, PR intervals and QRS

• ST segment depression is seen during the recovery phase of the transient ischemic events

abnormal systemic arterial blood pressure ( J:78066 )

• do not show a drop in blood pressure with pinacidil administration or any response to glyburide as in wild-type

hypertension ( J:78066 )

increased systemic arterial diastolic blood pressure ( J:78066 )

• seen in conscious 12- to 18-week old mice

increased systemic arterial systolic blood pressure ( J:78066 )

• seen in conscious 12- to 18-week old mice

abnormal vascular smooth muscle physiology ( J:78066 )

• glibenclamide-sensitive K_ATP current is absent in aortic smooth muscle cells

coronary artery spasm ( J:78066 )

• exhibit transient, repeated episodes of coronary artery vasospasm

• calcium channel antagonists reduce coronary artery vasospasms

muscle

abnormal vascular smooth muscle physiology ( J:78066 )

• glibenclamide-sensitive K_ATP current is absent in aortic smooth muscle cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
coronary artery disease		DOID:3393	OMIM:300464 OMIM:607339 OMIM:608316 OMIM:608318 OMIM:608320 OMIM:610947 OMIM:611139 OMIM:612030 OMIM:614293	J:78066