Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease

Christina Zuern, L. Krenács, Stephanie Starke, Jutta Heimrich, Alois Palmetshofer, Bettina Holtmann, Michael Sendtner, Tobias Fischer, Jan Galle, Christoph Wanner, Stefan Seibold

Research output: Contribution to journalArticle

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Abstract

The microtubule associated tumor suppressor gene 1 (MTUS1) is a recently published tumor suppressor gene, which has also been shown to act as an early component in the growth inhibitory signaling cascade of the angiotensin II type 2 receptor (AT2R). In this study we report the generation of MTUS1 knock-out (KO) mice, which develop normally but reveal higher body weights and slightly decreased blood pressure levels. Twenty-eight percent of the studied MTUS1 KO mice also developed heart hypertrophy and 12% developed nephritis, independent of blood pressure levels. Forty-three percent of the MTUS1 KO mice revealed lymphoid hyperplasia affecting spleen (20%), kidney (37%), lung (23%), lymph nodes (17%), and liver (17%) accompanied with leukocytosis, lymphocytosis, and mild anemia. One animal (3%) developed a marginal zone B-cell lymphoma affecting submandibular salivary gland and regional lymph nodes. The symptoms of all mentioned animals are consistent with a B-cell lymphoproliferative disease with features of systemic lupus erythematosus. In addition, body weight of the MTUS1 KO mice was significantly increased and isolated skin fibroblasts showed increased cell proliferation and decreased cell size, compared to wild-type (WT) fibroblasts in response to depleted FCS concentration and lack of growth factors. In conclusion we herein report the first generation of a MTUS1 KO mouse, developing spontaneous heart hypertrophy and increased cell proliferation, confirming once more the anti-proliferative effect of MTUS1, and a SLE-like lymphoproliferative disease suggesting crucial role in regulation of inflammation. These MTUS1 KO mice can therefore serve as a model for further investigations in cardiovascular disease, autoimmune disease and carcinogenesis.

Original languageEnglish
Pages (from-to)1079-1088
Number of pages10
JournalInternational Journal of Oncology
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Cardiomegaly
Tumor Suppressor Genes
Microtubules
Gene Knockout Techniques
Knockout Mice
Neoplasms
Fibroblasts
Lymph Nodes
Body Weight
Cell Proliferation
Angiotensin Type 2 Receptor
Blood Pressure
Lymphocytosis
Marginal Zone B-Cell Lymphoma
Nephritis
Submandibular Gland
Leukocytosis
Salivary Glands
Cell Size
Systemic Lupus Erythematosus

Keywords

  • AT2 receptor
  • ATBP
  • ATIP
  • Carcinogenesis
  • Hypertrophy
  • Lymphoma
  • MTSG1
  • Proliferation
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease. / Zuern, Christina; Krenács, L.; Starke, Stephanie; Heimrich, Jutta; Palmetshofer, Alois; Holtmann, Bettina; Sendtner, Michael; Fischer, Tobias; Galle, Jan; Wanner, Christoph; Seibold, Stefan.

In: International Journal of Oncology, Vol. 40, No. 4, 04.2012, p. 1079-1088.

Research output: Contribution to journalArticle

Zuern, C, Krenács, L, Starke, S, Heimrich, J, Palmetshofer, A, Holtmann, B, Sendtner, M, Fischer, T, Galle, J, Wanner, C & Seibold, S 2012, 'Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease', International Journal of Oncology, vol. 40, no. 4, pp. 1079-1088. https://doi.org/10.3892/ijo.2011.1311
Zuern, Christina ; Krenács, L. ; Starke, Stephanie ; Heimrich, Jutta ; Palmetshofer, Alois ; Holtmann, Bettina ; Sendtner, Michael ; Fischer, Tobias ; Galle, Jan ; Wanner, Christoph ; Seibold, Stefan. / Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease. In: International Journal of Oncology. 2012 ; Vol. 40, No. 4. pp. 1079-1088.
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