Principal investigator: Jeanette Nilsson/Gunnar Bjursell |
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Members of the group: Marie Kannius Jansson, Katja Madeyski, Ulf Lidberg, Sara Bengtsson, Eva Johansson
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Description of projects |
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The lactating mammary gland and pancreas synthese and secrete a bile salt stimulated lipase, called carboxyl ester lipase (CEL). The function of CEL is to play role in the intestinal absorption of dietary lipids and fat-soluble vitamins. We have in our research group isolated and characterized both the human and the mouse gene. We have also shown that there exists a transcribed truncated CEL pseudogene in the human genome. This pseudogene has compared to the CEL gene lost both the expression level and the tissue specificity. Recently, we have isolated human cosmid clones. When these were mapped they were shown to include both genes, located in a head to tail orientation approximately 11 kb apart with CEL as the most 5' one. By determining the nucleotide sequence of the region surrounding the genes it was possible to suggest a mechanism by which the CEL pseudogene was generated. The mechanism involves an over-replication of the gene, followed by a transposition-like event. As a result a new copy of the gene has been inserted, upstream the original position. This insertion has resulted in formation of a long duplicated sequence at the "host-insertion" boundary. Later during evolution the ancestral gene has become nonfuctional depending on a large deletion and some distinct mutations leading to loss of tissue specificity and expression level . Our interest is now focused on the transcriptional control of the CEL gene and on the identification of elements and corresponding factors which are important for the regulation both in mammary gland and pancreas. The CEL system is a good model for identifying various regulatory elements/transcriptions factors because the gene is constitutively expressed in pancreas, and in another tissue, the mammary gland, the gene is induced during pregnancy. By doing comparative studies both between the two tissues and with the different promoters (human wt, pseudogene and the mouse gene) is it possible to identify tissue specific transcription factors as well as factors important for the developmental process. Ongoing research is focused on the characterization of some such factors (NF-1 and Stat 5a/b) and involve cells of pancreatic as well as mammary gland origin, organ cultures and transgenic animals. |
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Publications
Department of Molecular Biology
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