Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante HST001 zur Verwendung für die nephrologische Forschung

Phenotypic and genotypic characterization of the ENU-induced mutant mouse line HST001 for use in nephrological research A dominant mutation was established in the line HST001 within the Munich ENU mouse mutagenesis project. On the genetic background of the inbred strain C3H heterozygous mutant mice showed a pathological increase of the plasma urea concentration. The phenotypic characterization of the mutant line included the measurement of body and organ weights, food intake and a broad spectrum of clinical chemical and hematological parameters as well as histological investigations of inner organs. For those examinations heterozygous mutant mice were mated to C3H mice and the offspring were divided in the two groups of mutant and wildtype littermates according to the concentration of plasma urea. The mutation showed complete phenotypic penetrance in all generations examined. In addition the genomic localization of the causative mutation was determined by linkage analysis. At the age of 4 weeks the body weight of the mutant mice and the wildtype mice showed no difference. After 6 weeks the mutant mice grew more slowly leading to a significantly lower body weight compared to the wildtype littermates. At the age of 26 weeks the body weight of mutant mice was about 20% reduced as compared to controls. Mutants also showed a reduction of the nose-rump-length and the body fat content. Regarding the relative organ weights the mutant mice showed significantly higher values for the spleen and the brain. The clinical-chemical and hematological parameters were determined in the animals at the age of 12, 18 and 24 weeks. The mutant mice had significantly higher plasma concentrations of urea and total protein as well as a higher activity of the alkaline phosphatase. Beside that they showed lower plasma concentrations of triglycerides and glucose and a lower activity of amylase than the wildtype mice. The mutants showed increasing plasma urea levels whereas the levels decreased in the controls. At the age of 24 weeks the mutants showed levels, which were two-fold higher than those of the controls. The histopathological investigation of the kidneys did not reveal any alterations, which could to explain the pathological increase of the plasma urea concentration in the mutant mice. However urea secretion via the kidneys was impaired, since the mutants showed significantly lower urine urea levels compared to the wildtype mice. The investigation of the hematological parameters resulted in the occurrence of altered values in the 18 und 24 weeks old mice. The mutant mice showed reduced numbers 91 of erythrocytes as well as decreased values for hemoglobin concentration, mean corpuscular volume and hematocrit. The hitherto existing results of the linkage analysis of the mutation in the genome using polymorphic microsatellite markers showed that the mutation maps to chromosome 7. This result has to be confirmed and specified by using additional markers and a larger number of animals.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2004

Author dc:creator

• Tran, Van Tuyen

Repository record source_url

https://edoc.ub.uni-muenchen.de/2257/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:2257