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Create a 10 pages page paper that discusses management 4900. It should state the result, its significance and any other conclusion(s), which may be relevant.

Introduction: A novel mouse mutant and the corresponding protein, mKIAA058 (in the following ‘KIAA’), was identified and further analysed. In order to understand the functions of this gene/protein, a mouse strain containing a non-functional allele (mKiAA058-. Null-allele) was successfully established. First data indicated an autosomal recessive inheritance as heterozygous (KIAA+/-) as well as homozygous knockout (KIAA-/-) animals were identified. The deficiency of this protein (‘Knockout KIAA’) affects multiple tissues, including skeletal defects (delayed/reduced development of bone and cartilage. growth retardation) as well as a progressive form of vascular degeneration. Later, a corresponding disease in humans was found in a small number of very young patients. The prospects of the patients are not clear at the time and the analysis of the mouse model may provide some hints for the severity of the disease. The analyses of the molecular mechanisms underlying the disease are still ongoing and some problems and experiments linked to these studies are given in the following. Statistical tests may be used to answer some of the questions.

In order to define potential effects of the presence/absence of the KIAA protein on the inheritance patterns, a number of breedings were performed. The genotypes of the parents were known and the genotypes of the litters (age: 14-16 days) were analysed by allele-specific PCR reactions.

In three parallel experiments (1.1, 1.2, 1.3), crossings of 5 wildtype males (KIAA+/+) with 10 heterozygous females (KIAA+/-) were started and all litters (given as total number of mice) were genotyped and the numbers of all possible genotypes are given in the following Table 1. All tested mice appear normal and show no altered phenotype at the tested age (day 14-16).

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