Phenotypes Associated with This Genotype

Genotype
MGI:3770254

• Allelic Composition: Tg(IGFBP1)2Miel/0
• Genetic Background: involves: C57BL * CBA

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

growth/size/body

decreased body weight ( J:128964 )

• at ~3 weeks, mice are ~10% lighter than wild-type littermates, but by 8 weeks of age, this difference is no longer statistically significant

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:84652 , J:128964 )

N • intraperitoneal glucose and insulin tolerance tests do not differ from wild-type results (J:84652)

N • fasting plasma lipoprotein, triglyceride, and free fatty acid levels do not differ from wild-type (J:84652)

N • fasting blood glucose and insulin levels at 16-20 weeks are similar to wild-type animals (J:128964)

abnormal glucose homeostasis ( J:128964 )

• hypoglycemic response to exogenous IGF-1 is attenuated in transgenic animals relative to controls

• blood glucose levels in transgenic mice are higher at all time points after glucose challenge but difference is significant only at 60 and 120 minutes

• initial increase in blood glucose in response to IGF-1 observed in wild-type males is abolished in transgenic males

• glucocompetence deteriorates with age

increased circulating glucose level ( J:128964 )

• at 40-44 weeks, males have increased fasting blood glucose levels

increased circulating insulin level ( J:84652 , J:128964 )

• mice exhibit a significantly greater hyperinsulinemic response to a glucose challenge than wild-type mice (J:84652)

• at 40-44 weeks, males have increased fasting insulin levels; fasting human IGFBP-1 levels are reduced reflecting relative hyperinsulinemia (J:128964)

impaired glucose tolerance ( J:128964 )

• 16-20 week-old mice show significant impairment in glucose tolerance compared to wild-type

• fasted mice challenged with IP injection of glucose show insulin levels that are 2.5 fold higher in transgenic males than control males at 30 minutes post-injection; insulin levels are 37% higher at 30 minutes in transgenic females relative to wild-type

• glucose/insulin rario is lower in transgenic males after glucose challenge relative to wild-type; males have higher 30-minute glucose and insulin levels compared with females

• ability to dispose of intraperitoneally administered glucose load is markedly impaired in aged mice compared to sex- and age-matched controls

cardiovascular system

decreased systemic arterial systolic blood pressure ( J:84652 )

• norm systolic blood pressure in fasted mutants does not differ from wild-type mice

• mutants experience a significant fall in pressure 30 minutes after intraperitoneal glucose challenge, but wild-type do not show this

decreased vasoconstriction ( J:84652 )

• magnitude of vasoconstriction response of aortic rings in transgenic mice to increasing concentrations of phenylephrine is significantly attenuated compared to wild-type mice (E_max1.13 g/mg in transgenics compared to 1.55 g/mg in wild-type)

• vasoconstriction in response to potassium chloride is reduced compared to wild-type

• when pre-constricted rings are incubated for 30 minutes with a nitric oxide inhibitor L-NMMA, rings from transgenic mice display a greater increment in tension than rings from wild-type mice

• norm relaxation of pre-constricted rings in response to vasodilators (acetycholine or sodium nitroprusside) is similar in both genotypes

muscle

decreased vasoconstriction ( J:84652 )

• magnitude of vasoconstriction response of aortic rings in transgenic mice to increasing concentrations of phenylephrine is significantly attenuated compared to wild-type mice (E_max1.13 g/mg in transgenics compared to 1.55 g/mg in wild-type)

• vasoconstriction in response to potassium chloride is reduced compared to wild-type

• when pre-constricted rings are incubated for 30 minutes with a nitric oxide inhibitor L-NMMA, rings from transgenic mice display a greater increment in tension than rings from wild-type mice

• norm relaxation of pre-constricted rings in response to vasodilators (acetycholine or sodium nitroprusside) is similar in both genotypes