IMPC: Phenotyping Cardiovascular Development of Rbms1-null mice

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The therapeutic stimulation of new blood vessel growth is considered a promising treatment for diseases in which organs become oxygen starved, for example after a heart attack or stroke and in diabetic vascular eye disease. Moreover, blood vessel function is thought to contribute to neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. However, we still have large gaps in our knowledge of how blood vessels normally grow to support the function of the brain, heart and other organs. Moreover, the first therapeutic attempts to stimulate vessel growth to alleviate oxygen starvation were ineffective, because the new vessels were not properly embedded into the organs they should supply. Based on prior work, we now know that two molecules called NRP1 and ITGB1 are essential to guide newly formed blood vessels to the right places in many organs. However, both molecules can also promote the formation of abnormal blood vessels and thereby exacerbate vascular problems in some diseases. Moreover, it is difficult to manipulate these molecules therapeutically, because they also participate in several other essential processes in the body. It is therefore important to identify additional molecules that function together with NRP1 and ITGB1 in blood vessel growth and may provide more selective targets for therapy. Our pilot studies suggest that a molecule termed RBMS1 functions together with NRP1 and ITGB1 in signalling pathways that support blood vessel growth. Moreover, mice lacking RBMS1 die before birth, demonstrating that its normal function is very important. However, very little is still known on the role of RBMS1 in normal cells, how it may support embryonic development and whether it plays a role in blood vessel growth by interacting with NRP1 and ITGB1 or in other pathways. We will therefore establish when during development RBMS1 deficiency causes death, determine which organ systems are affected and examine whether blood vessel growth is defective when RBMS1 is missing.