Transgenic Research

, Volume 19, Issue 5, pp 829–840

Functional evaluation of therapeutic response for a mouse model of medulloblastoma

  • Aislynn K. Samano
  • Sachiko Ohshima-Hosoyama
  • Thomas G. Whitney
  • Suresh I. Prajapati
  • Aoife Kilcoyne
  • Eri Taniguchi
  • William W. Morgan
  • Laura D. Nelon
  • Ai-Ling Lin
  • Osamu Togao
  • Inkyung Jung
  • Brian P. Rubin
  • Brent M. Nowak
  • Timothy Q. Duong
  • Charles Keller
Original Paper

DOI: 10.1007/s11248-010-9361-1

Cite this article as:
Samano, A.K., Ohshima-Hosoyama, S., Whitney, T.G. et al. Transgenic Res (2010) 19: 829. doi:10.1007/s11248-010-9361-1

Abstract

Medulloblastoma is an aggressive childhood cerebellar tumor. We recently reported a mouse model with conditional deletion of Patched1 gene that recapitulates many characteristics of the human medulloblastoma. Qualitative symptoms observed in the mouse model include irregular stride length, impaired cranial nerve function and decreased motor coordination and performance. In our current study, several quantitative behavioral assays including a mouse rotarod, a forced air challenge, a screen inversion test, a horizontal wire test, and stride length analysis were evaluated to determine the most sensitive and cost-effective functional assay for impaired neuromotor behavior associated with disease progression. Magnetic resonance imaging (MRI) was used to confirm and monitor tumor growth and as an anatomical biomarker for therapeutic response. Wild type mice or medulloblastoma-prone, conditional Patched1 knockout mice were observed by behavioral assays and MRI from postnatal weeks 3–6. Bortezomib treatment was administered during this period and therapeutic response was assessed using cerebellar volumes at the end of treatment. Of the behavioral tests assessed in this study, stride length analysis was best able to detect differences between tumor-prone mice and wild type mice as early as postnatal day 37 (P = 0.003). Significant differences between stride lengths of bortezomib treated and control tumor-bearing mice could be detected as early as postnatal day 42 (P = 0.020). Cerebellar volumes measured by MRI at the end of treatment validated the therapeutic effects seen by behavioral tests (P = 0.03). These findings suggest that stride length analysis may serve as one of the more sensitive and cost-effective method for assessing new therapeutic compounds in this and other preclinical model of brain tumors.

Keywords

MedulloblastomaGenetically-engineered mouse modelBrain tumorMRICerebellum

Supplementary material

11248_2010_9361_MOESM1_ESM.pdf (122 kb)
Supplementary material 1 (PDF 122 kb)
11248_2010_9361_MOESM2_ESM.pdf (223 kb)
Supplementary material 2 (PDF 223 kb)
11248_2010_9361_MOESM3_ESM.pdf (299 kb)
Supplementary material 3 (PDF 299 kb)
11248_2010_9361_MOESM4_ESM.pdf (297 kb)
Supplementary material 4 (PDF 296 kb)
11248_2010_9361_MOESM5_ESM.pdf (385 kb)
Supplementary material 5 (PDF 385 kb)

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Aislynn K. Samano
    • 1
    • 2
  • Sachiko Ohshima-Hosoyama
    • 1
  • Thomas G. Whitney
    • 3
  • Suresh I. Prajapati
    • 1
  • Aoife Kilcoyne
    • 1
  • Eri Taniguchi
    • 1
  • William W. Morgan
    • 2
  • Laura D. Nelon
    • 1
  • Ai-Ling Lin
    • 5
  • Osamu Togao
    • 6
  • Inkyung Jung
    • 4
  • Brian P. Rubin
    • 7
  • Brent M. Nowak
    • 3
  • Timothy Q. Duong
    • 5
  • Charles Keller
    • 1
    • 2
    • 8
  1. 1.Greehey Children’s Cancer Research InstituteUniversity of Texas Health Science CenterSan AntonioUSA
  2. 2.Department of Cellular & Structural BiologyUniversity of Texas Health Science CenterSan AntonioUSA
  3. 3.Department of Mechanical EngineeringUniversity of Texas at San AntonioSan AntonioUSA
  4. 4.Department of BiostatisticsUniversity of Texas Health Science CenterSan AntonioUSA
  5. 5.Research Imaging InstituteUniversity of Texas Health Science CenterSan AntonioUSA
  6. 6.Advanced Medical and Research CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  7. 7.Department of Anatomic Pathology, Cleveland ClinicTaussig Cancer Center and the Lerner Research InstituteClevelandUSA
  8. 8.Department of PediatricsUniversity of Texas Health Science CenterSan AntonioUSA