An investigation into morphological and biochemical abnormalities in the central nervous system of the mutant mouse tottering
Isaacs, Krystyna Renata
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https://hdl.handle.net/2142/19676
Description
Title
An investigation into morphological and biochemical abnormalities in the central nervous system of the mutant mouse tottering
Author(s)
Isaacs, Krystyna Renata
Issue Date
1993
Doctoral Committee Chair(s)
Abbott, Louise C.
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Anatomy
Biology, Neuroscience
Language
eng
Abstract
The mutant mouse tottering carries an autosomal recessive single gene mutation on chromosome 8 that produces three distinct neurological disorders shortly before weaning: petit mal or absence-like seizures, ataxia and intermittent movement disorders. The majority of the research on the mutant mouse tottering has concentrated on investigating the petit mal component of the neurological triad while overlooking the significant motor behavior abnormalities. This dissertation compared the morphology of developing and adult cerebella and the distribution patterns of calcium binding proteins throughout the motor systems of the brain, in two related murine mutants (tottering (tg/tg) and tottering/leaner ($tg/tg\sp{\rm la}$)) and normal age-matched mice.
The first portion of the dissertation was designed to investigate whether any previously reported abnormalities in the cerebellum of the mutant mice were present prior to the onset of behavioral symptoms. By using a second mutation, Oligosyndactyly (Os), that produces fused digits, and thereby allows the identification of mutants at birth, we determined that the brain weight and the thickness of the molecular layer and the size of Purkinje cell somata in the paramedian lobule of the cerebellum were significantly reduced in both mutants after, but not prior, to the onset of the symptoms. Using unbiased, stereologically correct methods, the volume of the entire cerebellum and volume of the molecular layer per Purkinje cell, but not the Purkinje cell number and density, were found to be reduced in adult mutant mice.
Evidence from the immunohistochemical analysis of the levels of three calcium binding proteins, calbindin, calretinin and parvalbumin, revealed differential staining between the mutant and wild type mice. Specifically, the motor cortex, basal ganglia and cerebellum, exhibited altered staining patterns in the mutant mice. In addition, the calcium binding proteins highlighted some structural abnormalities which had not been seen with other staining methods, namely torpedoes in the Purkinje cell axons of mutant mice.
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