Deficits in cerebellum-dependent learning and cerebellar morphology in male and female BTBR autism model mice.
Recently, there has been increased interest in the role of the cerebellum in autism spectrum disorders (ASD). To better understand the pathophysiological role of the cerebellum in ASD, it is necessary to have a variety of mouse models that have face validity for cerebellar disruption in humans. Here, we add to the literature on the cerebellum transgenic and induced mouse models of autism with the characterization of the cerebellum in the BTBR T+Itpr3tf/J (BTBR) inbred mouse strain, which has behavioral phenotypes that are suggestive of ASD in patients. When we examined both male and female BTBR mice in comparison to C57BL/6J (C57) controls, we noted that both sexes of BTBR mice showed motor coordination deficits characteristic of cerebellar dysfunction, but only the male mice showed differences in delay eyeblink conditioning, a cerebellum-dependent learning task that is also disrupted in ASD patients. Both male and female BTBR mice showed considerable expansion of and abnormal foliation in the cerebellum vermis--including significant expansion of specific lobules in the anterior cerebellum. In addition, we found a slight but significant decrease in Purkinje cell density in both male and female BTBR mice, irrespective of lobule. Furthermore, there was a marked reduction of Purkinje cell dendritic spines density in both male and female BTBR mice. These findings suggest that, for the most part, the BTBR mouse model successfully phenocopies many of the characteristics of the subpopulation of ASD patients that have a hypertrophic cerebellum. We discuss the significance of strain differences in the cerebellum as well as the importance of this first effort to identify both concordances and difference between male and female BTBR mice with regard to the cerebellum.
Pubmed ID: 37366488 RIS Download
Research resources used in this publication
- GraphPad Prism (RRID:SCR_002798) (software resource)
- ImageJ (RRID:SCR_003070) (software resource)
- Allen Mouse Brain Reference Atlas (RRID:SCR_013286) (data or information resource)
- Compresstome VF-300 (RRID:SCR_018452) (instrument resource)
- MATLAB (RRID:SCR_001622) (software resource)
- Python Programming Language (RRID:SCR_008394) (software resource)
- Picospritzer III (RRID:SCR_018152) (instrument resource)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
- BTBR (RRID:MGI:2160299) (organism)
Additional research tools detected in this publication
None foundAntibodies used in this publication
None foundAssociated grants
- Agency: NIGMS NIH HHS, United States
Id: P20 GM103443
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This is a list of tools and resources that we have found mentioned in this publication.
GraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsImageJ (software resource)
RRID:SCR_003070
Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsAllen Mouse Brain Reference Atlas (data or information resource)
RRID:SCR_013286
Allen Mouse Brain Atlas includes full color, high resolution anatomic reference atlas accompanied by systematic, hierarchically organized taxonomy of mouse brain structures. Enables interactive online exploration of atlas and to provide deeper level of 3D annotation for informatics analysis and viewing in Brain Explorer 3D viewer.
View all literature mentionsCompresstome VF-300 (instrument resource)
RRID:SCR_018452
Vibrating microtome for cutting tissue slices, similar to cryostats and vibrating microtomes. Fully automated for sectioning fixed and live tissues, with down to 1 um precision. Can cut tissue slice thicknesses ranging from 3 um to 2000 um, at 1 um intervals.
View all literature mentionsMATLAB (software resource)
RRID:SCR_001622
Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsPython Programming Language (software resource)
RRID:SCR_008394
Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.
View all literature mentionsPicospritzer III (instrument resource)
RRID:SCR_018152
Intracellular microinjection dispense system by Parker Hannifin. Supplies repeatable pressure pulses. Designed for rapid and reproducible ejections of picoliter and nanoliter volumes used in conjunction with intracellular or extracellular studies while avoiding inherent desensitization of nerve cells which accompanies Iontophoretic methodology. System comes complete with high speed valves and necessary tubing assemblies.
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsBTBR (organism)
RRID:MGI:2160299
laboratory mouse with name BTBR from MGI.
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