Systemic overexpression of growth hormone (GH) in transgenic FVB/N inbred mice: an optimized model for holistic studies of molecular mechanisms underlying GH-induced kidney pathology.
Transgenic mice overexpressing growth hormone (GH) display a plethora of phenotypic alterations and provide unique models for studying and influencing consequences of chronic GH excess. Since the first report on GH transgenic mice was published in 1982, many different mouse models overexpressing GH from various species at different levels and with different tissue specificities were established, most of them on random-bred or hybrid genetic background. We have generated a new transgenic mouse model on FVB/N inbred background, expressing bovine (b) GH under the control of the chicken beta-actin promoter (cbetaa). cbetaa-bGH transgenic mice exhibit ubiquitous expression of bGH mRNA and protein and circulating bGH levels in the range of several microg/ml, resulting in markedly stimulated growth and the characteristic spectrum of pathological lesions which were described in previous GH overexpressing mouse models. Importantly, a consistent sequence of renal alterations is observed, mimicking progressive kidney disease in human patients. The novel, genetically standardized GH transgenic mouse model is ideal for holistic transcriptome and proteome studies aiming at the identification of the molecular mechanisms underlying GH-induced pathological alterations especially in the kidney. Moreover, genetically defined cbetaa-bGH mice facilitate random mutagenesis screens for modifier genes which influence the effects of chronic GH excess and associated pathological lesions.
von Waldthausen
Dagmar C
DC
Institute of Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Strasse 25, Munich, Germany.
Schneider
Marlon R
MR
Renner-Müller
Ingrid
I
Rauleder
Dirk N
DN
Herbach
Nadja
N
Aigner
Bernhard
B
Wanke
Rüdiger
R
Wolf
Eckhard
E
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D002417:Cattle; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000502:physiology*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010957:Plasmids; D011401:Promoter Regions, Genetic
D013006:Growth Hormone