title: Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone. Studies in transgenic mice.
abstract: BACKGROUND
  Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia.
  
  
  METHODS
  The aim of this study was to determine if body growth and glomerulosclerosis were mediated by different bGH regions. Amino acid substitutions in the bGH alpha-helix III were generated, and lines of transgenic mice that expressed these products were developed. Female transgenic mice carrying the native bGH gene (bGH mice), a mutated bGH gene that encodes a destabilized alpha-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic alpha-helix III (bGH-E117L, G119R, A122D; bGH-m8 mice) were examined at 2-3 months and 6-9 months of age. Body, kidney, and heart weights were measured. Urinary glucose, albumin, creatinine, and serum glucose were measured in all mice. Serum levels of insulin-like growth factor I (IGF-I) were measured in the 2-3 month group. Whole blood hemoglobin A1 was measured in some mice of the 6-9 month group. Kidney sections were examined by light and immunofluorescence microscopy. Glomerular volume was measured and related to body weight by allometry.
  
  
  RESULTS
  The bGH-m11 mice developed glomerulosclerosis indistinguishable from that seen in bGH transgenic mice, even though they had normal body size. Glomerular growth exceeded body growth by allometry in both bGH and bGH-m11 strains. bGH-m8 mice had glomeruli of appropriate size and normal histologic appearance; however, they were dwarfs. IGF-I was increased in bGH mice; they also had an increased albumin/creatinine ratio at 6-9 months. None of the mice were hyperglycemic.
  
  
  CONCLUSIONS
  These data indicated that development of glomerulosclerosis and body growth promotion were mediated by different regions of the growth hormone molecule. The glomerular response to bGH was unique and consisted of increased size and glomerulosclerosis.
authors.affiliation: Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: C W
authors.initials: CW
authors.lastname: Yang
authors.forename: L J
authors.initials: LJ
authors.lastname: Striker
authors.forename: C
authors.initials: C
authors.lastname: Pesce
authors.forename: W Y
authors.initials: WY
authors.lastname: Chen
authors.forename: E P
authors.initials: EP
authors.lastname: Peten
authors.forename: S
authors.initials: S
authors.lastname: Elliot
authors.forename: T
authors.initials: T
authors.lastname: Doi
authors.forename: J J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: G E
authors.initials: GE
authors.lastname: Striker
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002417:Cattle; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000473:pathology; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D051381:Rats; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone