Phenotypes Associated with This Genotype

Genotype
MGI:3764985

• Allelic Composition: Mc2r^tm1Dchi/Mc2r^tm1Dchi
• Genetic Background: B6.129P2-Mc2r^tm1Dchi

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

Histological analysis of the adrenal gland of Mc2r^tm1Dchi/Mc2r^tm1Dchi mice

mortality/aging

postnatal lethality, incomplete penetrance ( J:127445 )

• three-quarters of mice die prior to weaning with most dying within the first 48 hours after birth likely due to hypoglycemia with decreased gluconeogenesis in the liver and defective neonatal nutritional adaptatio

• while most mice that display reduced glucose levels die by day 7 mice that maintained normal glucose levels survive

homeostasis/metabolism

decreased circulating adrenaline level ( J:127445 )

• 0.12+/-0.02 ng/ml compared to 0.72+/-0.14 ng/ml in heterozygotes and 0.59+/-0.08 ng/ml in wild-type mice

• however, norephrinepherine and dopamine levels are normal

decreased circulating corticosterone level ( J:127445 )

• corticosterone serum levels are undetectable in male mice

• fasting mice do not display increased corticosterone levels as wild-type mice do

decreased circulating aldosterone level ( J:127445 )

• 104+/-25 pg/ml compared to 343+/-103 pg/ml in wild-type mice

increased circulating adrenocorticotropin level ( J:127445 )

• 1394+/-89 pg/ml compared to 370+/-50 pg/ml in heterozygotes and 281+/-106 pg/ml in wild-type mice

• response to adrenocorticotropin is defective

increased circulating potassium level ( J:127445 )

• in female mice

abnormal glucose homeostasis ( J:127445 )

• blood glucose levels decline faster after a 36-hour fast compared to in wild-type mice (45.8+/-11.7 mg/dl compared to 79.2+/-9.5 mg/dl in wild-type mice)

hypoglycemia ( J:127445 )

• at P0.5, 13 of 14 mice are hypoglycemic and 12 of 14 mice had glucose levels below 20 mg/dl

• however, while most mice that display reduced glucose levels die by day 7 mice maintained normal glucose levels survive

abnormal gluconeogenesis ( J:127445 )

• gluconeogenesis is impaired

increased circulating chloride level ( J:127445 )

• in male mice

endocrine/exocrine glands

abnormal adrenal gland zona fasciculata morphology ( J:127445 )

• in adulthood, zona fasciculata cells exhibit an increase number of lipid droplets and inactive mitochondrial compared to wild-type mice

• however, zona glomerulosa cells are normal and adrenal glands of newborn mice are normal

abnormal adrenal gland capsule morphology ( J:127445 )

• in adulthood, the thickness of the adrenal capsule is increased compared to in wild-type mice

adrenal gland hypoplasia ( J:127445 )

• 0.58+/-0.02 mg per pair compared to 2.24+/-0.18 mg per pair in wild-type mice

• while cell number is not reduced cell size is compared to in wild-type adrenal glands

increased thymus weight ( J:127445 )

behavior/neurological

lethargy ( J:127445 )

• some mice are pale and lethargic at birth

adipose tissue

decreased total body fat amount ( J:127445 )

cardiovascular system

decreased heart rate ( J:127445 )

• heart rate is decreased

• however, blood pressure is normal

hematopoietic system

increased thymus weight ( J:127445 )

increased spleen weight ( J:127445 )

immune system

increased thymus weight ( J:127445 )

increased spleen weight ( J:127445 )

growth/size/body

increased spleen weight ( J:127445 )