title: Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis.
abstract: The insulin receptor substrates (IRSs) function in insulin signaling. Four members of the family, IRS-1 through IRS-4, are known. Previously, mice with targeted disruption of the genes for IRS-1, -2, and -3 have been characterized. To examine the physiological role of IRS-4, we have generated and characterized mice lacking IRS-4. Male IRS-4-null mice were approximately 10% smaller in size than wild-type male mice at 9 wk of age and beyond, whereas the female null mice were of normal size. Breeding pairs of IRS-4-null mice reproduced less well than wild-type mice. IRS-4-null mice exhibited slightly lower blood glucose concentration than the wild-type mice in both the fasted and fed states, but the plasma insulin concentrations of the IRS-4-null mice in the fasted and fed states were normal. IRS-4-null mice also showed a slightly impaired response in the oral glucose tolerance test. Thus the absence of IRS-4 caused mild defects in growth, reproduction, and glucose homeostasis.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: V R
authors.initials: VR
authors.lastname: Fantin
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: G E
authors.initials: GE
authors.lastname: Lienhard
authors.forename: S R
authors.initials: SR
authors.lastname: Keller
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006128:Growth / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D012098:Reproduction / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C491531:Irs4 protein, mouse; D010750:Phosphoproteins