Phenotypes associated with this allele

• Allele Symbol: Gucy2c^tm1Gar
• Allele Name: targeted mutation 1, David L Garbers
• Allele ID: MGI:2665316
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gucy2c^tm1Gar/Gucy2c^tm1Gar	B6.129S6-Gucy2c^tm1Gar	MGI:5300906
hm2	Gucy2c^tm1Gar/Gucy2c^tm1Gar	either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6J)	MGI:2665347

Genotype
MGI:5300906

hm1

• Allelic Composition: Gucy2c^tm1Gar/Gucy2c^tm1Gar
• Genetic Background: B6.129S6-Gucy2c^tm1Gar

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

adipose tissue

increased subcutaneous adipose tissue amount ( J:178241 )

increased total body fat amount ( J:178241 )

• mutants exhibit an accumulation of adipose mass, including an increase in visceral and subcutaneous fat compartments

behavior/neurological

increased compensatory feeding amount ( J:178241 )

• fasted and refed mutants display deficient postprandial satiation

polyphagia ( J:178241 )

• mutants are hyperphagic, independent of sex, dietary nutrients, or dietary caloric content

• however, mutants exhibit normal lipid digestion, lipid absorption, distribution and clearance, normal energy mobilization and expenditure, normal circadian cycles and thermoregulatory reflexes to cold, indicating that an increase in caloric consumption is the probable cause of the excess adiposity

cardiovascular system

increased heart weight ( J:178241 )

cardiac hypertrophy ( J:178241 )

• mean heart size in mice raised on either the low calorie or high calorie diet is increased compared to wild-type mice

growth/size/body

increased heart weight ( J:178241 )

cardiac hypertrophy ( J:178241 )

• mean heart size in mice raised on either the low calorie or high calorie diet is increased compared to wild-type mice

increased body weight ( J:178241 )

• mutants raised on a standard low calorie diet, moderate calorie diet, or high calorie diet exhibit an increased body weight compared to wild-type mice

• females raised on the high calorie diet showed the highest weight increase, with mutants being 26.3% heavier than wild-type mice

homeostasis/metabolism

increased circulating insulin level ( J:178241 )

• fasted serum concentrations of 12 months old mutants raised on a high caloric diet are increased compared to wild-type mice on the same diet

increased circulating leptin level ( J:178241 )

• fasted serum leptin levels are increased at 10-12 and 18 months of age in mutants raised on either the low calorie or high calorie diet

impaired glucose tolerance ( J:178241 )

• impaired glycemic control

increased liver triglyceride level ( J:178241 )

• mice raised on a low calorie diet exhibit increased hepatic triglyceride content

integument

increased subcutaneous adipose tissue amount ( J:178241 )

liver/biliary system

increased liver triglyceride level ( J:178241 )

• mice raised on a low calorie diet exhibit increased hepatic triglyceride content

hepatic steatosis ( J:178241 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:178241
obesity		DOID:9970	OMIM:601665	J:178241

Genotype
MGI:2665347

hm2

• Allelic Composition: Gucy2c^tm1Gar/Gucy2c^tm1Gar
• Genetic Background: either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6J)

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:43046 )

• following inoculation with enterotoxigenic E. coli strain 1676 by gavage, most homozygotes survived to weaning, whereas all wild-type and heterozygous controls died within 72 hrs of infection

• only a small minority of homozygotes died within 24-72 hrs of administration of E. coli strain 1676; however, no diarrhea was observed and no cause of death was established

• following inoculation with a human enterotoxigenic E. coli strain (H10407) which does not colonize and infect mice, 23 of 26 homozygotes survived to weaning, while the remaining 3 died within 24 hrs of the gavage

immune system

decreased susceptibility to bacterial infection ( J:43046 )

• following inoculation with enterotoxigenic E. coli strain 1676 by gavage, homozygotes failed to develop signs of diarrhea, indicating resistance to enterotoxigenic bacteria that produce heat stable enteroxins

• following an oral inoculum of 10 U of E. coli heat-stable enterotoxin, 3-day suckling homozygotes failed to exhibit any fluid accumulation within the intestinal lumen, as determined by gut/carcass weight ratio

• in contrast, suckling homozygotes showed normal fluid accumulation within the intestine following oral inoculation with 5 ug of cholera toxin

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:43046 )

• following inoculation with enterotoxigenic E. coli strain 1676 by gavage, most homozygotes survived to weaning, whereas all wild-type and heterozygous controls died within 72 hrs of infection

• only a small minority of homozygotes died within 24-72 hrs of administration of E. coli strain 1676; however, no diarrhea was observed and no cause of death was established

• following inoculation with a human enterotoxigenic E. coli strain (H10407) which does not colonize and infect mice, 23 of 26 homozygotes survived to weaning, while the remaining 3 died within 24 hrs of the gavage

digestive/alimentary system

diarrhea ( J:43046 )

• following oral inoculation with 5 ug of cholera toxin, suckling homozygotes show normal fluid accumulation within the intestine (diarrhea), as determined by gut/carcass weight ratio