Phenotypes Associated with This Genotype

Genotype
MGI:3579026

• Allelic Composition: Mc4r^tm1Dhu/Mc4r^tm1Dhu
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

growth/size/body

increased susceptibility to diet-induced obesity ( J:69814 )

• slower metabolic response to higher fat in the diet as measured by VO2

increased body size ( J:38224 )

• increased body length at 19 weeks, disregarding tails

increased body weight ( J:38224 , J:94617 )

• weight normal until after 4 weeks of age (J:38224)

• by 5 weeks most mice were heavier than controls (J:38224)

• after 7 weeks, all mice were heavier than controls, by 50% for males and 2 fold for females (J:38224)

• conventionally housed mice are heavier than controls and heavier than mice with free access to a running wheel (J:94617)

• rapidly gain weight when no longer able to exercise but weight gain is reversed somewhat if opportunity to exercise is restored (J:94617)

behavior/neurological

abnormal food intake ( J:102986 )

• the stress of isolation inhibits feeding

polyphagia ( J:38224 , J:94617 )

• hyperphagia (J:38224)

• food consumption in females increased by 46% (J:38224)

• food consumption normal when given free access to a running wheel but become hyperphagic when access to running wheels is removed (J:94617)

abnormal locomotor activation ( J:94617 )

• tended to exercise somewhat less than controls when given access to a running wheel

abnormal circadian behavior phase ( J:94617 )

• more active in daylight

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:69814 )

• slower metabolic response to higher fat in the diet as measured by VO2

increased circulating leptin level ( J:38224 )

• levels elevated 1.5X in males and 4.5X in females at 4-8 weeks of age

• levels elevated 2.5X in males and 6.5X in females at 17-23 weeks of age

abnormal glucose homeostasis ( J:38224 )

hyperglycemia ( J:38224 )

• in males only by 10-14 weeks of age

• at 17-23 weeks of age male blood glucose levels are 2X normal

increased circulating insulin level ( J:38224 )

• hyperinsulinemia in both males and females

• levels increased 5 fold in males and 9 fold in females at 4-8 weeks of age

• at 17-23 weeks of age levels increased to 14X normal in males and to 60X normal in females

reproductive system

reduced fertility ( J:94617 )

• conventionally housed animals reproduced poorly, far fewer litters

• reproduced almost as well as controls when able to exercise

skeleton

decreased osteoclast cell number ( J:97566 )

• reduced number of osteoclasts

increased bone mass ( J:97566 )

• exhibit high bone mass at 6 months of age

hematopoietic system

decreased osteoclast cell number ( J:97566 )

• reduced number of osteoclasts

immune system

decreased osteoclast cell number ( J:97566 )

• reduced number of osteoclasts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:38224