Phenotypes Associated with This Genotype

Genotype
MGI:3783343

• Allelic Composition: Stat3^tm1Flv/Stat3^tm1Flv; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: C57BL/6 * SJL

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

Neural-specific STAT3 deletion results in severe obesity in Stat3^tm1Flv/Stat3^tm1Flv Tg(Nes-cre)1Kln/0 mice similar to that seen in Lepr^db/Lepr^db mice

mortality/aging

neonatal lethality, incomplete penetrance ( J:89242 )

• reducing the number of pups to lower the competition for milk rescues a substantial proportion of mutants from neonatal lethality

growth/size/body

obese ( J:89242 )

• mutants that survive the neonatal period develop obesity by 6-9 weeks of age and weigh twice as much as controls as adults

decreased body length ( J:89242 )

• mutants are about 8% shorter than controls

enlarged liver ( J:89242 )

liver/biliary system

enlarged liver ( J:89242 )

hepatic steatosis ( J:89242 )

adipose tissue

increased total body fat amount ( J:89242 )

• total fat content is increased 5-fold compared to controls, however lean mass is unchanged

abnormal brown adipose tissue morphology ( J:89242 )

• brown adipose tissue becomes diffuse and the structure resembles white adipose tissue

abnormal white adipose tissue morphology ( J:89242 )

• white adipose cells are larger in mutants

homeostasis/metabolism

impaired adaptive thermogenesis ( J:89242 )

• after a 12 hour fast mutants become hypothermic, however this is reversed after 1.5 hours of refeeding

• mutants housed at 4 degrees C for 3.5 hours cannot maintain their body temperature like wild-type and drop about 1 degree in body temperature every 30 min until they reach 34 degrees C, at which point they stabilize this temperature, indicating decreased sympathetic activity

increased circulating corticosterone level ( J:89242 )

increased circulating leptin level ( J:89242 )

increased circulating triglyceride level ( J:89242 )

decreased body temperature ( J:89242 )

• in the fed state, mutants show a slight but significantly lowered body temperature

abnormal body temperature homeostasis ( J:89242 )

• in the fed state, mutants show a slight but significantly lowered body temperature, however mutants are able to stabilize their body temperature by consuming twice as much food

decreased energy expenditure ( J:89242 )

abnormal glucose homeostasis ( J:89242 )

hyperglycemia ( J:89242 )

• plasma fasting glucose concentrations are increased

increased circulating insulin level ( J:89242 )

• plasma insulin concentrations are as much as 14- and 10-fold higher in the fed and fasted state, respectively

impaired glucose tolerance ( J:89242 )

• plasma glucose and insulin concentrations increase 5-fold after glucose challenge compared to controls

insulin resistance ( J:89242 )

• plasma insulin concentrations are as much as 14- and 10-fold higher in the fed and fasted state, respectively, indicating insulin resistance

behavior/neurological

decreased food intake ( J:89242 )

• pups contain reduced amount of milk in stomachs

polyphagia ( J:89242 )

• mutants consume twice as much food as wild-type

• administration of a malanocortin-3/4 receptor, MTII, reverses their hyperphagia over a 4 hour period

endocrine/exocrine glands

small seminal vesicle ( J:89242 )

♂

absent corpus luteum ( J:89242 )

♀

small testis ( J:89242 )

♂

reproductive system

small seminal vesicle ( J:89242 )

♂

absent corpus luteum ( J:89242 )

♀

small testis ( J:89242 )

♂

short uterine horn ( J:89242 )

♀ • reduced size of uterine horns

anovulation ( J:89242 )

♀ • corpa lutea are never observed indicating that ovulation does not occur

female infertility ( J:89242 )

♀

male infertility ( J:89242 )

♂