Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Ogueta, Samuel; Olazabal, Isabel M.; Santos, Izabelle Barcellos; Delgado-Baeza, Emilio; Jp, Garcia-Ruiz

doi:10.1677/joe.0.1650321

Cited by 36 publications

(16 citation statements)

References 35 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collectively, these data indicate that the proliferative capacity of T cells was markedly altered in transgenic as compared to control mice, with major age-dependent differences. Considering that B cells were not changed in transgenic mice overexpressing b-GH, according with the data reported by MAR-TINKO et al (11), it can be concluded that GH differentially affects immune cell number and its function in the spleen and may also affect the development of autoimmune diseases like arthritis (14).…”

Section: Discussionsupporting

confidence: 53%

Efecto de la sobreexpresión de GH sobre la actividad de las células T en ratones transgénicos

Esquifino

Arce

Álvarez

et al. 2002

J. Physiol. Biochem.

View full text Add to dashboard Cite

Growth hormone plays a key role in the maturation and maintenance of the immune response, however, the effects of chronic high circulating concentrations of the hormone on the immune system is poorly understood. Transgenic mice overexpressing bovine growth hormone (b-GH) gene, fused to the rat phosphoenolpyruvate carboxykinase promoter (PEPCK), with very high plasma concentration of heterologous b-GH and their littermate normal siblings were used. Spleen cellularity, percentages of total T lymphocytes, CD4+ and CD8+ cells, ratio of T cell subpopulations, mitogen-induced lymphocyte proliferation and natural killer (NK) cell activity were examined in male transgenic mice and normal littermate mice at 2 and 6 months of age. The number of splenic lymphocytes was greater in transgenic mice than in matched normal littermates at both ages. The NK cell activity was lower in transgenic mice than in the matched normal littermates at both ages, with the lowest values found in older mice. The b-GH transgenic mice had lower percentages of T cells at both ages, however, in young transgenic mice, the percentage of CD4+ cells was reduced while percentage of CD8+ cells was increased in comparison to normal controls. Both basal and mitogen-induced proliferation capacity of splenocytes were reduced in PEPCK-b-GH-25 mice as compared to normal littermates of both ages. Proliferative indexes in response to concanavalin A and phytohemagglutinin were markedly decreased in 6 month old PEPCK-b-GH-25 mice as compared to littermate controls or younger mice. These results indicate that overexpression of b-GH in mice is associated with decreased T cell function and that these abnormalities are age-dependent.

show abstract

Section: Discussionsupporting

confidence: 53%

Efecto de la sobreexpresión de GH sobre la actividad de las células T en ratones transgénicos

Esquifino

Arce

Álvarez

et al. 2002

J. Physiol. Biochem.

View full text Add to dashboard Cite

show abstract

“…Serum samples were obtained from three WT and three WIP −/− mice sacrificed at 16 (two mice) and at 28 (one mouse) weeks of age. The positive control for autoantibodies was obtained from transgenic mice expressing bovine growth hormone 16. NIH3T3 murine fibroblasts were subjected to immunofluorescence as previously reported 17.…”

Section: Methodsmentioning

confidence: 99%

WIP null mice display a progressive immunological disorder that resembles Wiskott–Aldrich syndrome

Curcio

Pannellini

Lanzardo

et al. 2006

The Journal of Pathology

View full text Add to dashboard Cite

The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome caused by mutations in the WAS protein (WASP). This participates in signalling and cytoskeletal homoeostasis, and some of its activities are regulated by its binding to the WASP interacting protein (WIP). WIP deficiency, however, has not yet been shown to be of pathological significance in humans. Here we show that, in WIP null (WIP(-/-)) mice, it produces haematological alterations and anatomical abnormalities in several organs, most probably as a consequence of autoimmune attacks. Granulocytosis and severe lymphopenia are associated with a proportional increase in segmented cells and fewer bone marrow erythrocytes and lymphocytes. Splenomegaly is accompanied by an increase of haematopoietic tissue and red pulp, reduction of the white pulp, and fewer B (B220(+)) lymphocytes (also apparent in the lymph nodes and Peyer's patches). Ulcerative colitis, interstitial pneumonitis, glomerular nephropathy with IgA deposits, autoantibodies, and joint inflammation are also evident. These progressive immunological disorders closely mimic those seen in WAS. WIP deficiency may thus be implicated in some cases in which mutations in the gene encoding WASP are not detected.

show abstract

“…The observation of mononuclear cell infiltration also suggests the presence of B cells. A report by Ogueta et al demonstrated the development of an arthritic disorder and expression of self-antibodies in transgenic mice expressing bGH under the transcriptional control of the phosphoenolpyruvate carboxykinase promoter, a different promoter from the one used in this study 35. Their findings suggested that the kidney damage seen in those mice might be due to an autoimmune-like process caused by the chronic high GH/IGF levels.…”

Section: Discussionmentioning

confidence: 60%

Identification of differentially expressed genes in the kidneys of growth hormone transgenic mice

Coschigano

Wetzel

Obichere

et al. 2010

Growth Hormone & IGF Research

View full text Add to dashboard Cite

Objective Bovine growth hormone (bGH) transgenic mice develop severe kidney damage. This damage may be due, at least in part, to changes in gene expression. Identification of genes with altered expression in the bGH kidney may identify mechanisms leading to damage in this system that may also be relevant to other models of kidney damage. Design cDNA subtraction libraries, northern blot analyses, microarray analyses and real-time reverse transcription polymerase chain reaction (RT/PCR) assays were used to identify and verify specific genes exhibiting differential RNA expression between kidneys of bGH mice and their non-transgenic (NT) littermates. Results Immunoglobulins were the vast majority of genes identified by the cDNA subtractions and the microarray analyses as being up-regulated in bGH. Several glycoprotein genes and inflammation-related genes also showed increased RNA expression in the bGH kidney. In contrast, only a few genes were identified as being significantly down-regulated in the bGH kidney. The most notable decrease in RNA expression was for the gene encoding kidney androgen-regulated protein. Conclusions A number of genes were identified as being differentially expressed in the bGH kidney. Inclusion of two groups, immunoglobulins and inflammation-related genes, suggests a role of the immune system in bGH kidney damage.

show abstract

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Cited by 36 publications

References 35 publications

Efecto de la sobreexpresión de GH sobre la actividad de las células T en ratones transgénicos

Efecto de la sobreexpresión de GH sobre la actividad de las células T en ratones transgénicos

WIP null mice display a progressive immunological disorder that resembles Wiskott–Aldrich syndrome

Identification of differentially expressed genes in the kidneys of growth hormone transgenic mice

Contact Info

Product

Resources

About