the min mouse : (1.)heterozygous for the highly penetrant apc min allele
DESCRIPTION
The MIN mouse : (1.)Heterozygous for the highly penetrant Apc Min allele. (2.) Min/Min homozygotes die at gastrulation. (3.)Mice develop numerous (50-200) adenomas in the small intestine, and few (0-3) in the colon. (4.)Death occurs around 5 months of age. - PowerPoint PPT PresentationTRANSCRIPT
The MIN mouse:
(1.) Heterozygous for the highly penetrant ApcMin allele.
(2.) Min/Min homozygotes die at gastrulation.
(3.) Mice develop numerous (50-200) adenomas in the small intestine, and few (0-3) in the colon.
(4.) Death occurs around 5 months of age.
(5.) Tumor multiplicity modulated by genetic background, drugs, and diet.
wnt
frizzled
dsh
conductin/axinGSK3 -catenin-catenin slimbP
APC
-catenin
LEF/ TCF
LEF/ TCF
Target Genes
-catenin
E-cadherin -catenin
100X
GROUP TUMOR #
4 wks 16 1 (N=25)
10 wks 23 7 (N=9)
15 wks 63 8 (N=7)
5-FU (410 wks) 7 4 (N=13)
RTX (410 wks) 114 60 (N=7)
5-FU/RTX (410 wks) 3 1 (N=12)
UntreatedTreated
(Tomudex 5mg/kg)Folate-deficient diet
Does the genetic character of stromal (i.e., bone marrow-derived) cells
determine response to anti-neoplastic agents?
MIN RecipienteGFP Donor
Transplant
Marrow response to drug ex vivo
Tumor response to drug therapy
Therapeutic toxicity
The role of the tumor stroma in conferring response to TS inhibitors.
Introduce TS gene
Bone Marrow
MARROW THERAPY TUMOR # p-VALUE
Normal - 32 ± 19
+ 8 ± 5 0.008
TS Overexpressing - 35 ± 22
+ 19 ± 23 0.183
