Targeted expression of des(1-3) human insulin-like growth factor I in transgenic mice influences mammary gland development and IGF-binding protein expression

Endocrinology. 1996 Jan;137(1):321-30. doi: 10.1210/endo.137.1.8536631.


To test the hypothesis that insulin-like growth factor I (IGF-I) regulates mammary gland development and lactation, the expression of both human (h) IGF-I and des(1-3)hIGF-I was targeted to the mammary gland in transgenic mice using a novel exon replacement strategy and the rat whey acidic protein (rWAP) gene regulatory sequences. Both transgenes expressed a 0.7-kilobase messenger RNA (mRNA). The abundance of WAP-IGE-I and WAP-DES mRNA on day 10 of lactation ranged from 0.2-1.0% and 0.2-13% of the endogenous mouse WAP mRNA, respectively. For WAP-DES mice, transgene expression was greatest from midpregnancy throughout lactation. Western blot analysis showed the presence of correctly processed hIGF-I in milk from these transgenic mice. This hIGF-I was capable of stimulating protein synthesis in cultured rat L6 myoblasts. Ligand blotting indicated changes in mammary gland secretion of IGFBP in response to WAP-DES expression. Histological analysis of mammary tissue from mice overexpressing des(1-3)hIGF-I showed incomplete mammary involution, ductile hypertrophy, and loss of secretory lobules associated with increased deposition of collagen. These changes are believed to occur through autocrine and paracrine effects of des(1-3)-hIGF-I on both epithelial and stromal cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Lactation
  • Mammary Glands, Animal / growth & development*
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Transgenic / genetics
  • Milk Proteins / genetics
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Tissue Distribution


  • Insulin-Like Growth Factor Binding Proteins
  • Milk Proteins
  • Oligonucleotide Probes
  • Peptide Fragments
  • RNA, Messenger
  • whey acidic proteins
  • insulin-like growth factor 1, des-(1-3)-
  • Insulin-Like Growth Factor I