Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante SMA002 als Tiermodell für Wachstumsdefizit und Hyperaktivität

This thesis describes the phenotypic and genotypic analysis of the dominant mutation in the ENU-induced mutant mouse line SMA002. The results were derived from the analysis of heterozygous mutant animals on the C3H genetic background. As the main phenotype of SMA002, an abnormal behavior combined with reduced body weight was revealed. The mutant phenotype showed complete penetrance in all generations analyzed. Abnormal behavior, as the most prominent phenotype was characterized by the occurrence of restlessness and an increased grooming behavior. The grooming behavior was increased fivefold but did not always contain all aspects of the standard repertoire. Pathological examinations of the skin and the analysis of parameters of the immune system indicated that this behavior was not caused by an allergic reaction. Clinical examination of the animals revealed a significant difference in body weight between mutant and control littermates. The body weight of the mutant animals was about 30% lower than control. In addition mutant animals had a significant lower nose-rump length and a significant lower carcass weight. Analysis of the peripheral blood for hematological and clinical chemical parameters as well as subsequent pathological examinations excluded a kidney, liver or pancreas disease as the potential cause of the abnormal phenotype. Decreased values for cholesterol, triglyceride, total protein and potassium in the mutant animals referred to an increased metabolism and a hormonal deviation in these mice. Furthermore, deviations of the IGF-system were found in the mutants. Linkage analysis of the causative mutation was carried out by genome wide polymorphic microsatellite marker analysis. The highest correlation for the mutation was found with the markers D13Mit20 (35cM) and D13Mit253 (37cM) of chromosome 13. This aberrant phenotype of the line SMA002 has not yet been reported. Thus, SMA002 represents a novel mouse model for the analysis of abnormal behavior and growth defects. Subsequent analysis will identify the exact mutation in the line. In addition, further analysis of the phenotype will result in detailed information on the metabolism and hormonal regulation of SMA002.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2004

Author dc:creator

• Howaldt, Maike Susanne

Repository record source_url

https://edoc.ub.uni-muenchen.de/1929/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:1929