Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone: Studies in transgenic mice

C. W. Yang, L. J. Striker, C. Pesce, W. Y. Chen, E. P. Peten, Sharon Elliot, T. Doi, J. J. Kopchick, G. E. Striker

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia. EXPERIMENTAL DESIGN: 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 α-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 α-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic α-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.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalLaboratory Investigation
Volume68
Issue number1
StatePublished - Jan 1 1993
Externally publishedYes

Fingerprint

Transgenic Mice
Growth
bovine growth hormone
Insulin-Like Growth Factor I
Genes
Creatinine
Body Weight
Kidney
Glucose
Obese Mice
Uremia
Body Size
Amino Acid Substitution
Fluorescence Microscopy
Serum Albumin
Growth Hormone
Albumins

Keywords

  • Allometry
  • Morphometry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yang, C. W., Striker, L. J., Pesce, C., Chen, W. Y., Peten, E. P., Elliot, S., ... Striker, G. E. (1993). Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone: Studies in transgenic mice. Laboratory Investigation, 68(1), 62-70.

Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone : Studies in transgenic mice. / Yang, C. W.; Striker, L. J.; Pesce, C.; Chen, W. Y.; Peten, E. P.; Elliot, Sharon; Doi, T.; Kopchick, J. J.; Striker, G. E.

In: Laboratory Investigation, Vol. 68, No. 1, 01.01.1993, p. 62-70.

Research output: Contribution to journalArticle

Yang, CW, Striker, LJ, Pesce, C, Chen, WY, Peten, EP, Elliot, S, Doi, T, Kopchick, JJ & Striker, GE 1993, 'Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone: Studies in transgenic mice', Laboratory Investigation, vol. 68, no. 1, pp. 62-70.
Yang, C. W. ; Striker, L. J. ; Pesce, C. ; Chen, W. Y. ; Peten, E. P. ; Elliot, Sharon ; Doi, T. ; Kopchick, J. J. ; Striker, G. E. / Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone : Studies in transgenic mice. In: Laboratory Investigation. 1993 ; Vol. 68, No. 1. pp. 62-70.
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abstract = "BACKGROUND: Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia. EXPERIMENTAL DESIGN: 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 α-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 α-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic α-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.",
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AU - Yang, C. W.

AU - Striker, L. J.

AU - Pesce, C.

AU - Chen, W. Y.

AU - Peten, E. P.

AU - Elliot, Sharon

AU - Doi, T.

AU - Kopchick, J. J.

AU - Striker, G. E.

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N2 - BACKGROUND: Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia. EXPERIMENTAL DESIGN: 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 α-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 α-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic α-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.

AB - BACKGROUND: Mice transgenic for bovine growth hormone (bGH) gene have increased body weight and severe glomerulosclerosis leading to death in uremia. EXPERIMENTAL DESIGN: 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 α-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 α-helix III (bGH-L121P, E126G; bGH-m11 mice), or a mutated bGH gene that encodes a perfect amphiphilic α-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.

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