title: Tumor burden and clonality in multiple intestinal neoplasia mouse/normal mouse aggregation chimeras.
abstract: Aggregation chimeras were formed between C57BL/6 mice heterozygous for the Apc(min) (Min) mutation and wild-type SWR mice, that differ in their Pla2g2a status, a modifier of Apc(min), and also in their resistance to intestinal polyp formation. Variation in the dolichos biflorus agglutinin-staining patterns of the intestines of these mouse strains was used to determine the chimeric composition of the intestine in individual mice and to examine the clonal composition of adenomas. Macroscopic adenoma numbers in chimeric mice were compared with the expected adenoma numbers based on the percentage of C57BL/6J-Apc(min/+) epithelium in individual mice. These results unexpectedly show that there was no apparent inhibitory effect of the SWR-derived (Pla2g2a wild-type) tissue on adenoma formation in the C57BL/6J-Apc(min/+) epithelium. This suggests that the main genetic modifiers of the Min phenotype act at a cellular or crypt-restricted level with no discernable systemic effect. All adenomas were seen to contain C57BL/6J-Apc(min/+)-derived epithelium, confirming that the germ-line mutation of the mApc gene is necessary to initiate tumorigenesis in this model system, and that the mApc gene acts in a cell autonomous fashion.
authors.affiliation: Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom. m.novelli@ucl.ac.uk
authors.forename: M R
authors.initials: MR
authors.lastname: Novelli
authors.forename: H
authors.initials: H
authors.lastname: Wasan
authors.forename: I
authors.initials: I
authors.lastname: Rosewell
authors.forename: J
authors.initials: J
authors.lastname: Bee
authors.forename: I P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: N A
authors.initials: NA
authors.lastname: Wright
authors.forename: W F
authors.initials: WF
authors.lastname: Bodmer
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D017931:DNA Primers; D005260:Female; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers