title: Genetic dissection of IGF1-dependent and -independent effects of permanent GH excess on postnatal growth and organ pathology of mice.
abstract: To study insulin-like growth factor 1 (IGF1)-independent effects of permanent growth hormone (GH) excess on body and organ growth and pathology in vivo, hemizygous bovine GH transgenic mice with homozygous disruption of the Igf1 gene (Igf1(-/-)/GH) were generated, and examined in comparison to Igf1(-/-), Igf1(+/-), wild-type (WT), Igf1(+/-)/GH, and GH mice. GH mice and Igf1(+/-)/GH mice showed increased serum IGF1 levels and the well-known giant-phenotype of GH transgenic mice. In contrast, the typical dwarf-phenotype of Igf1(-/-) mice was only slightly ameliorated in Igf1(-/-)/GH mice. Similar to GH mice, Igf1(-/-)/GH mice displayed hepatocellular hypertrophy, glomerulosclerosis, and reduced volumes of acidophilic cells in the pituitary gland. However, GH excess associated skin lesions of male GH mice were not observed in Igf1(-/-)/GH mice. Therefore, development of GH excess induced liver-, kidney-, and pituitary gland-alterations in GH transgenic mice is independent of IGF1 whereas GH stimulated body growth depends on IGF1.
authors.affiliation: Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, Veterinärstr. 13, 80539 Munich, Germany. Electronic address: blutke@patho.vetmed.uni-muenchen.de.
authors.forename: A
authors.initials: A
authors.lastname: Blutke
authors.affiliation: Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
authors.forename: M R
authors.initials: MR
authors.lastname: Schneider
authors.affiliation: Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Renner-Müller
authors.affiliation: Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, Veterinärstr. 13, 80539 Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Herbach
authors.affiliation: Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, Veterinärstr. 13, 80539 Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wanke
authors.affiliation: Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000172:Acromegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002417:Cattle; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D019076:Transgenes
chemical_list: C073294:growth hormone, bovine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: GH; Growth; IGF1; Mouse; Organ pathology