Original Paper

Transgenic Research

, Volume 19, Issue 5, pp 829-840

First online:

Functional evaluation of therapeutic response for a mouse model of medulloblastoma

  • Aislynn K. SamanoAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science CenterDepartment of Cellular & Structural Biology, University of Texas Health Science Center
  • , Sachiko Ohshima-HosoyamaAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science Center
  • , Thomas G. WhitneyAffiliated withDepartment of Mechanical Engineering, University of Texas at San Antonio
  • , Suresh I. PrajapatiAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science Center
  • , Aoife KilcoyneAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science Center
  • , Eri TaniguchiAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science Center
  • , William W. MorganAffiliated withDepartment of Cellular & Structural Biology, University of Texas Health Science Center
  • , Laura D. NelonAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science Center
  • , Ai-Ling LinAffiliated withResearch Imaging Institute, University of Texas Health Science Center
    • , Osamu TogaoAffiliated withAdvanced Medical and Research Center, University of Texas Southwestern Medical Center
    • , Inkyung JungAffiliated withDepartment of Biostatistics, University of Texas Health Science Center
    • , Brian P. RubinAffiliated withDepartment of Anatomic Pathology, Cleveland Clinic, Taussig Cancer Center and the Lerner Research Institute
    • , Brent M. NowakAffiliated withDepartment of Mechanical Engineering, University of Texas at San Antonio
    • , Timothy Q. DuongAffiliated withResearch Imaging Institute, University of Texas Health Science Center
    • , Charles KellerAffiliated withGreehey Children’s Cancer Research Institute, University of Texas Health Science CenterDepartment of Cellular & Structural Biology, University of Texas Health Science CenterDepartment of Pediatrics, University of Texas Health Science Center Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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

Medulloblastoma Genetically-engineered mouse model Brain tumor MRI Cerebellum