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.