The aim of this programme is to gain insight into the causes and effects of developmental disorders and congenital malformations. Various methods are employed.
The first subprogramme (a) attempts - on the basis of the genotype - to clone relevant genes and to analyse their products, and to define the process leading to the associated (abnormal) phenotype.
The next two subprogrammes (b,c) are based on an existing and inbred, or a toxicologically induced abnormal phenotype, respectively, and attempt to map the genotype and associated gene products.
Subprogramme (d) assesses the long-term medical, psychosocial and socially relevant effects of the treatment of congenital malformations.
Aims of subprogrammes:
a. To elucidate the development of the caudal hindbrain and its neural crest at the molecular level. This requires the cloning of relevant genes, analysis of their function, and ultimately the elucidation of how they are linked in a cascade of cell signalling and transcriptional regulation. Our strategy to find the genes consists of the use of spontaneously occurring genetic anomalies that correlate with congenital malformations of the pharyngeal arches (e.g. Hirschsprung's disease and DiGeorge syndrome).
b. Pathophysiologic and genetic characterization of the development of chronic renal insufficiency, and its possible prevention and treatment. Mainly the spontaneously hypertensive fawn-hooded (FHH) rat strain is used, which develops proteinuria and kidney damage at an early age spontaneously and dies prematurely from end-stage renal failure. The susceptibility to develop renal damages is influenced by at least five genes, named Rf-1 to Rf-5. Main efforts are currently directed at identification and functional characterization of Rf-1 on rat chromosome 1.
c. The role of hormones and that of the genes expressed during normal and abnormal lung development are studied in a reproducible rat model of abnormal lung development induced by Nitrofen, and in transgenic mice, and in organotypic cultures of embryonic lung buds.
d. Evaluation, somatically and psychosocially (quality of life), of diagnostics, treatment of congenital malformations, especially related to parental support, nutritional assessment and pain management in pediatric surgical patients in the perioperative period. |
