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

  • Authors:
    • Christina Zuern
    • Laszlo Krenacs
    • Stephanie Starke
    • Jutta Heimrich
    • Alois Palmetshofer
    • Bettina Holtmann
    • Michael Sendtner
    • Tobias Fischer
    • Jan Galle
    • Christoph Wanner
    • Stefan Seibold
  • View Affiliations

  • Published online on: December 20, 2011     https://doi.org/10.3892/ijo.2011.1311
  • Pages: 1079-1088
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zuern C, Krenacs L, Starke S, Heimrich J, Palmetshofer A, Holtmann B, Sendtner M, Fischer T, Galle J, Wanner C, Wanner C, et al: Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease. Int J Oncol 40: 1079-1088, 2012
APA
Zuern, C., Krenacs, L., Starke, S., Heimrich, J., Palmetshofer, A., Holtmann, B. ... Seibold, S. (2012). Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease. International Journal of Oncology, 40, 1079-1088. https://doi.org/10.3892/ijo.2011.1311
MLA
Zuern, C., Krenacs, L., Starke, S., Heimrich, J., Palmetshofer, A., Holtmann, B., Sendtner, M., Fischer, T., Galle, J., Wanner, C., Seibold, S."Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease". International Journal of Oncology 40.4 (2012): 1079-1088.
Chicago
Zuern, C., Krenacs, L., Starke, S., Heimrich, J., Palmetshofer, A., Holtmann, B., Sendtner, M., Fischer, T., Galle, J., Wanner, C., Seibold, S."Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease". International Journal of Oncology 40, no. 4 (2012): 1079-1088. https://doi.org/10.3892/ijo.2011.1311