Phenotypes Associated with This Genotype

Genotype
MGI:5014260

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Gh1-cre)bKnmn/0
• Genetic Background: involves: 129 * C57BL/6 * FVB

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

mortality/aging

lethality, incomplete penetrance ( J:173444 )

• litters from F3 generation mutant dams are smaller than those from cre-negative dams or mutants from the F1or F2 generations; litter size of female mutants of the F1 or F2 generations conform to the expected size

growth/size/body

increased lean body mass ( J:173444 )

• 10 month-old F3 females show a significant increase in lean body mass; 3.5 month-old males and females and 10 month-old males do not exhibit any increase

increased body weight ( J:173444 )

• growth rates are identical to controls up to 3 months of age but mean body weights for F3 generation males and females diverge from controls at 4 and 6.5 months, respectively

• at 9 months, F3 females are 46% heavier than controls but after 9 months, females lose weight with the average weight no longer being different from controls; males are significantly heavier than controls by 4 months of age with the difference continuing throughout life (at least 12-13 months)

obese ( J:173444 )

• F3 male mutants develop obesity with age

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:173444 )

N • serum leptin and insulin levels are not different from controls in 3-4 month-old F3 males or females (all young adult groups even if group contained obese animals); no changes are observed in serum Igf1 levels

increased circulating leptin level ( J:173444 )

• leptin levels rise with obesity in older male and female mutants

decreased circulating growth hormone level ( J:173444 )

• levels are reduced by 72% in F3 generation adult males and by 50% in F3 female adults

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:173444 )

N • despite reduction in GH-positive somatotroph numbers, there is no change in overall number of pituitary cells, or changes in pituitary size or morphology

decreased somatotroph cell number ( J:173444 )

• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells

adipose tissue

increased total body fat amount ( J:173444 )

• some F3 generation animals were analyzed by DEXA (dual-energy x-ray absorptiometry) to look for changes in fat and lean mass

• 3.5 month-old F3 males show signficantl increases in grams of body fat; females show significant increases in fat mass at 3.5 and (in a small subset) at 10 months

nervous system

decreased somatotroph cell number ( J:173444 )

• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells

reproductive system

reproductive system phenotype ( J:173444 )

N • timing of puberty is normal in mutants