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POSTER 159 - PHENOTYPIC AND GENETIC ANALYSIS OF THE INTESTINAL LENGTHENING IN PRM/ALF MICE
Aubin-Houzelstein G
INRA, Maisons-Alfort
Co-Authors: 1)-2) Da Silva N R, 1) Bellier S, 1) Salaün
P, 3) Montagutelli X, 1) Panthier J J
Institutions: 1) INRA, Maisons-Alfort 2) Present
organisation: MRC, Edinburgh 3) Institut Pasteur, Paris
PRM/Alf inbred mice exhibit a selective intestinal lengthening. Indeed, PRM/Alf intestine is one third longer compared to other inbred strains (C57BL6/J, C3H/He, DBA/2J and 129S2). The phenotype is acquired mostly during the postnatal period, before weaning. Interestingly, the gastrointestinal transit time, as evaluated using thermophilic Bacillus subtilis.spores as an inert marker, is identical in PRM/Alf and other inbred mice, thus implying an increase in transit speed. Physiologic analysis showed that mechanical contractions and slow-wave activity are increased in PRM/Alf proximal small intestine compared to controls. Since the intestinal electrical pacemaker activity originates in the interstitial cells of Cajal (ICC), the distribution of ICC in small intestine and colon segments of PRM/Alf mice and controls was analysed. We found that the ICC number is increased in small intestine and colon of PRM/Alf mice compared to controls.
We studied the genetic determinism of intestine lengthening in PRM/Alf. We found that it is polygenic. It also involves a strong maternal effect. Cross-fostering experiments revealed that the dam's genotype acts synergistically with the offspring's genotype to confer the longest intestine. Moreover, genes in the offspring have a direct effect on intestine length.
Altogether, PRM/Alf is a unique model associating a considerable intestine lengthening and an accelerated digestive transit. This model may prove useful for the identification of intestinotrophic molecules that could be of clinical relevance in postoperative management of small and large bowel resections in humans. It also uncovers the possible role of milk content in the control of intestine length.
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