Mice hemizygous for the hIGFBP-1 transgene are viable and fertile with no reported gross morphological or developmental changes. The hIGFBP-1 transgene encompasses the entire human IGFBP-1 structural gene and its regulatory sequences, allowing transgene expression of IGFBP-1 to remain responsive to normal hormonal regulation. Transgenic mice overexpress hIGFBP-1, with hIGFBP-1 mRNA expression in a tissue-specific fashion more similar to the human pattern than the murine pattern. Fasting transgenic mice have elevated total serum IGFBP-1 levels that fluctuate according to nutritional status (as they do in humans), and exhibit postprandial hyperinsulinemia with preservation of normal glucocompetence and insulin sensitivity. Transgenic mice also have significantly greater hyperinsulinemic response to glucose challenge and cardiovascular abnormalities in response to carbohydrate load and vasoconstrictors. Transgenic mice exhibit fasting hyperglycemia and hyperinsulinemia and glucose intolerance in later life. The phenotype of hIGFBP-1 overexpressing mice may vary between male and female mice. These hIGFBP-1 transgenic mice may be useful in studying metabolic and vascular homeostasis, diabetes, and the role of insulin-like growth factor binding protein in placentation and preeclampsia.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As these mice were originally characterized on both C57BL/CBA mixed and CBA congenic backgrounds, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
