Identification of Intestinotrophic Factors in Mouse Milk

S Bellier, S. Andrei, G Aubin-Houzelstein, C. Beauvallet, N Da Silva, P. Martin, G. Miranda, X Montagutelli, J J Panthier, JM Vanderwinden

How does an organ grow to a specific size? Is size regulation specific for each organ? George Cuvier (1835) stated, in what is commonly referred to as the law of coexistence, that “a living organism is a unique and self-contained whole. All of its parts are mutually related and cooperate for the same purpose. Although no part can change unless the others also change, each part considered separately suffices to indicate the others”. PRM/Alf mice stand in contradiction to this law. They exhibit an obvious and selective lengthening of the intestine; their intestine is 74.8 ± 5.3 cm long compared with 51.0 ± 3.0 cm in other inbred mice, such as DBA2/J. This unusual phenotype is acquired postnatally, before weaning. The trait is polygenic and involves a strong maternal effect. Indeed, the dam’s genotype account for approximately 50% of the length difference between PRM/Alf mice and mice from other inbred strains. Two mutually non-exclusive mechanisms were proposed to explain the maternal effect. First, the gut microbial community (microbiota) of PRM/Alf mice, which is transmitted from the mother to its pups, contains one or several micro-organisms responsible, either directly or not, for the lengthening of the intestine. Second, the milk of PRM/Alf females contains one or several intestinotrophic factors. To identify such factors present in the milk of mice, we have set up an integrative approach in the genomic and proteomic areas. Milk proteins with intestinotrophic properties could contribute to the well-being and health of consumers, have repercussions in the field of reconstituted infant formulas, and contribute to human medicine by helping patients to recover a normal intestinal function after surgical resection.