Phenotypes associated with this allele

• Allele Symbol: Tg(Vil1-cre/ERT2)23Syr
• Allele Name: transgene insertion 23, Sylvie Robine
• Allele ID: MGI:3053826
• Summary: 55 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543691
cn2	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543696
cn3	Csnk1a1^tm1.1Ybn/Csnk1a1^+ Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543694
cn4	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543693
cn5	Tcf7l1^tm1Efu/Tcf7l1^tm1Efu Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * DBA/2	MGI:5430370
cn6	Tcf7^tm1Cle/Tcf7^tm1Cle Tcf7l1^tm1Efu/Tcf7l1^tm1Efu Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * DBA/2	MGI:5430371
cn7	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448982
cn8	Apc^tm1Tno/Apc^+ Rac3^tm1.1Bea/Rac3^tm1.1Bea Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6715667
cn9	Myo5b^tm1.1Cle/Myo5b^tm1.1Cle Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * DBA/2	MGI:5790964
cn10	Apc^tm2.1Cip/Apc^+ Atg7^tm1Tchi/Atg7^tm1Tchi Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj * DBA/2	MGI:5702420
cn11	Pten^tm2Mak/Pten^tm2Mak Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3829450
cn12	Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5430368
cn13	Tcf7^tm1Cle/Tcf7^tm1Cle Tcf7l1^tm1Efu/Tcf7l1^tm1Efu Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5430369
cn14	Slc39a4^tm2Gka/Slc39a4^tm2Gka Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5438021
cn15	Pou5f1^tm1Scho/Pou5f1^tm1Scho Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3772216
cn16	Vps35^tm1.1Hckn/Vps35^tm1.1Hckn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5749127
cn17	Apc^tm2.1Cip/Apc^tm2.1Cip Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5702422
cn18	Apc^tm2.1Cip/Apc^+ Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5702414
cn19	Slc39a5^tm1Gka/Slc39a5^tm1Gka Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5581458
cn20	Rbpj^tm1Hon/Rbpj^tm1Hon Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3603010
cn21	Lgr4^tm1.1Knis/Lgr4^tm1.1Knis Lgr5^tm2.1Cle/Lgr5^tm2.1Cle Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5285825
cn22	Btrc^tm1Paga/Btrc^tm1Paga Fbxw11^tm1Ybn/Fbxw11^tm1Ybn Tg(Vil1-cre/ERT2)23Syr/?	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5568951
cn23	Btrc^tm1Paga/Btrc^+ Fbxw11^tm1Ybn/Fbxw11^tm1Ybn Tg(Vil1-cre/ERT2)23Syr/?	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5568952
cn24	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm3.1Tyj/Trp53^tm3.1Tyj	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448987
cn25	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm2.1Tyj/Trp53^tm2.1Tyj Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6448984
cn26	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448985
cn27	Slc39a7^tm1.1Tfk/Slc39a7^tm1.1Tfk Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5902447
cn28	Apc^Min/Apc^+ Trp53^tm2.1Tyj/Trp53^tm2.1Tyj Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2	MGI:6448989
cn29	B3gnt6^tm1Lx/B3gnt6^tm1Lx C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2	MGI:5902497
cn30	Tle5^tm1.1Mmt/Tle5^tm1.1Mmt Apc^tm1Mmt/Apc^+ Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S2/SvPas * C57BL/6 * DBA * SJL	MGI:4888016
cn31	Rpap3^tm1c(KOMP)Wtsi/Rpap3^tm1c(KOMP)Wtsi Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6N * DBA/2	MGI:7310427
cn32	Slc40a1^tm2Nca/Slc40a1^tm2Nca Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3771553
cn33	Tfrc^tm3.1Nca/Tfrc^tm3.1Nca Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * DBA/2	MGI:5689323
cn34	Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5608788
cn35	Xbp1^tm2Glm/Xbp1^tm2Glm Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5559518
cn36	Gt(ROSA)26Sor^tm4(HIF2A*)Kael/Gt(ROSA)26Sor^tm4(HIF2A*)Kael Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:6721388
cn37	Xbp1^tm3Glm/Xbp1^tm3Glm Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5441534
cn38	Numb^tm1Zili/Numb^tm1Zili Tg(Vil1-cre/ERT2)23Syr/?	involves: 129/Sv * C57BL/6	MGI:5699005
cn39	Nr5a2^tm1Sjns/Nr5a2^tm1Sjns Tg(Vil1-cre/ERT2)23Syr/?	involves: 129/Sv * C57BL/6 * DBA/2 * SJL	MGI:3721528
cn40	Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw Cdc25b^tm1Pjd/Cdc25b^tm1Pjd Tg(Vil1-cre/ERT2)23Syr/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:4941917
cn41	Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw Cdc25b^tm1Pjd/Cdc25b^tm1Pjd Cdc25c^tm1Hpw/Cdc25c^tm1Hpw Tg(Vil1-cre/ERT2)23Syr/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:4941918
cn42	Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw Tg(Vil1-cre/ERT2)23Syr/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:4941915
cn43	Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw Cdc25c^tm1Hpw/Cdc25c^tm1Hpw Tg(Vil1-cre/ERT2)23Syr/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:4941916
cn44	Cdc25b^tm1Hpw/Cdc25b^tm1Pjd Tg(Vil1-cre/ERT2)23Syr/0	involves: 129X1/SvJ * C57BL/6 * DBA/2	MGI:4943329
cn45	Btnl1^em3Ahay/Btnl1^em3Ahay Btnl6^em2Ahay/Btnl6^em2Ahay Tg(Vil1-cre/ERT2)23Syr/0	involves: BALB/c * C57BL/6J * DBA/2	MGI:7545317
cn46	Hprt1^tm2(CAG-mCherry/Villin*)Syr/? Vil1^tm1Syr/Vil1^tm1Syr Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6	MGI:5512865
cn47	Hprt1^tm1(CAG-mCherry/Villin)Syr/? Vil1^tm1Syr/Vil1^tm1Syr Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6	MGI:5512864
cn48	Tg(Vil1-cre/ERT2)23Syr/0 Zmiz1^tm1c(EUCOMM)Hmgu/Zmiz1^tm1c(EUCOMM)Hmgu	involves: C57BL/6 * C57BL/6N * DBA/2	MGI:5795900
cn49	Slc5a6^tm1.1Said/Slc5a6^tm1.1Said Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:6721401
cn50	Lima1^tm1Blsg/Lima1^+ Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:6192735
cn51	Lima1^tm1Blsg/Lima1^tm1Blsg Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:6192734
cn52	Rnf43^tm1Cle/Rnf43^tm1Cle Znrf3^tm1Cle/Znrf3^tm1Cle Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:5439367
cn53	Btnl1^em4Ahay/Btnl1^em4Ahay Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:7545313
cn54	Rpap3^tm1c(KOMP)Wtsi/Rpap3^tm1c(KOMP)Wtsi Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6N * DBA/2	MGI:7310426
tg55	Tg(Vil1-cre/ERT2)23Syr/0	involves: C57BL/6 * DBA/2	MGI:6401286

Genotype
MGI:5543691

cn1

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

increased apoptosis ( J:204886 )

• in the gut following tamoxifen treatment

increased fibroblast apoptosis ( J:204886 )

• in mouse embryonic fibroblasts following tamoxifen treatment

Genotype
MGI:5543696

cn2

• Allelic Composition: Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj; Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

neoplasm

increased carcinoma incidence ( J:204886 )

• tamoxifen-treated mice exhibit severe dysplasia and intramucosal carcinomas throughout the small bowel

digestive/alimentary system

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

cellular

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

Genotype
MGI:5543694

cn3

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1⁺; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

neoplasm

increased carcinoma incidence ( J:204886 )

• within 6 months, 7 of 9 tamoxifen-treated mice develop invasive carcinomas that permeates the bowel muscular wall into the subserosal fat with some involvement of the serosal surface (stage T4)

Genotype
MGI:5543693

cn4

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

mortality/aging

premature death ( J:204886 )

• after 2 weeks of tamoxifen treatment

neoplasm

increased carcinoma incidence ( J:204886 )

• widespread high-grade dysplasia and numerous intramucosal carcinomas invading the lamina propria in most of the small-bowel crypts and villi within 2 weeks of tamoxifen treatment

digestive/alimentary system

abnormal enterocyte proliferation ( J:204886 )

• increased proliferation after tamoxifen treatment throughout the crypt-villus axis

cellular

increased apoptosis ( J:204886 )

• in the gut of tamoxifen treated mice but no more so than in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil-cre/ERT2)23Syr mice

abnormal enterocyte proliferation ( J:204886 )

• increased proliferation after tamoxifen treatment throughout the crypt-villus axis

Genotype
MGI:5430370

cn5

• Allelic Composition: Tcf7l1^tm1Efu/Tcf7l1^tm1Efu; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:185753 )

N • tamoxifen-treated mice exhibit normal adult intestinal homeostasis

Genotype
MGI:5430371

cn6

• Allelic Composition: Tcf7^tm1Cle/Tcf7^tm1Cle; Tcf7l1^tm1Efu/Tcf7l1^tm1Efu; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:185753 )

N • tamoxifen-treated mice exhibit normal adult intestinal homeostasis

Genotype
MGI:6448982

cn7

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the entire bowel

• distal gut dysplasia appears later than in mice with Trp53^tm2.1Tyj (containing the R172H missense mutation)

abnormal intestine development ( J:291671 )

• jejunal and ileal organoids exhibit increased proliferation, decreased differentiation, and resemble highly dysplastic spheroids

abnormal enterocyte morphology ( J:291671 )

• high-grade dysplasia in the entire bowel

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

endocrine/exocrine glands

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the entire bowel

• distal gut dysplasia appears later than in mice with Trp53^tm2.1Tyj (containing the R172H missense mutation)

Genotype
MGI:6715667

cn8

• Allelic Composition: Apc^tm1Tno/Apc⁺; Rac3^tm1.1Bea/Rac3^tm1.1Bea; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA/2

digestive/alimentary system

decreased alimentary system tumor incidence ( J:306088 )

• reduced number of intestinal tumors in duodenum and jejunum

• normal number of intestinal tumors in ileum and colon

decreased intestinal adenoma incidence ( J:306088 )

• reduced number of intestinal tumors in duodenum and jejunum

neoplasm

decreased tumor growth/size ( J:306088 )

• tumors less proliferative

• reduced ability to form colonies from single tumor cells in vitro

abnormal tumor susceptibility ( J:306088 )

• median intestinal tumor-free survival 138 vs 171 days

decreased alimentary system tumor incidence ( J:306088 )

• reduced number of intestinal tumors in duodenum and jejunum

• normal number of intestinal tumors in ileum and colon

decreased intestinal adenoma incidence ( J:306088 )

• reduced number of intestinal tumors in duodenum and jejunum

Genotype
MGI:5790964

cn9

• Allelic Composition: Myo5b^tm1.1Cle/Myo5b^tm1.1Cle; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * DBA/2

Microvillus inclusion disease phenotype in Myo5b^tm1.1Cle/Myo5b^tm1.1Cle Tg(Vil1-cre/ERT2)23Syr/0 mice

digestive/alimentary system

diarrhea ( J:227079 )

• tamoxifen induced mice exhibit watery diarrhea

abnormal intestinal epithelium morphology ( J:227079 )

• tamoxifen induced mice show intestinal crypt hyperplasia

• intercellular spaces between enterocytes are enlarged in tamoxifen induced mice

abnormal enterocyte morphology ( J:227079 )

• PAS-positive vesicles (secretory granules) are seen in crypt enterocytes and at the crypt-villus transition of tamoxifen treated mice

abnormal small intestinal villus morphology ( J:227079 )

• mature villus enterocytes show clusters of subapical vesicles, autolysosomes, and microvillus inclusions on day 4 after tamoxifen induction

• marker analysis indicates disturbed basolateral polarity of villus enterocytes in tamoxifen treated mice

• subapical accumulation of secretory granules precedes occurrence of microvillus inclusions

abnormal small intestinal microvillus morphology ( J:227079 )

• intestines show a severe reduction to almost complete absence of apical microvilli on day 4 after tamoxifen induction

fused small intestinal villi ( J:227079 )

• tamoxifen treated mice exhibit fusion of intestinal villi

small intestinal villus atrophy ( J:227079 )

• mice show intestinal villus atrophy on day 4 after tamoxifen induction

growth/size/body

weight loss ( J:227079 )

• mice exhibit severe weight loss starting from day 3 after tamoxifen induction

homeostasis/metabolism

dehydration ( J:227079 )

• tamoxifen induced mice exhibit dehydration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microvillus inclusion disease		DOID:0060775	OMIM:251850	J:227079

Genotype
MGI:5702420

cn10

• Allelic Composition: Apc^tm2.1Cip/Apc⁺; Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj * DBA/2

neoplasm

decreased intestinal adenoma incidence ( J:227287 )

• tamoxifen treated mice show fewer and smaller colonic tumors that develop more slowly and have a lower proliferation rate than in single conditional Apc heterozygous mice

• however, prolonged antibiotic treatment of tamoxifen treated mice induces numerous intestinal tumor foci and tamoxifen treated mice administered anti-CD8 antibodies to induce partial depletion of Treg show increased tumor development

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:227287 )

• abnormal accumulation of granules of mucus in goblet cells in the tumor-free mucosa of tamoxifen treated mice

abnormal Paneth cell morphology ( J:227287 )

• unusually small in tumor-free mucosa of tamoxifen treated mice

decreased intestinal adenoma incidence ( J:227287 )

• tamoxifen treated mice show fewer and smaller colonic tumors that develop more slowly and have a lower proliferation rate than in single conditional Apc heterozygous mice

• however, prolonged antibiotic treatment of tamoxifen treated mice induces numerous intestinal tumor foci and tamoxifen treated mice administered anti-CD8 antibodies to induce partial depletion of Treg show increased tumor development

abnormal gut flora balance ( J:227287 )

• tamoxifen treated mice show altered distribution of gut bacteria, with bacteria occasionally seen within the crypt compartment of the small intestine

• tamoxifen treated mice show a difference in the overall composition of both fecal and ileal microbiota compared to single conditional Apc heterozygotes, with mice showing a high level of Gram+ bacteria related to Firmicutes and low levels of Proteobacteria in feces

• ileal mucosa of tamoxifen treated mice has a higher bacterial diversity than single conditional Apc heterozygotes

abnormal intestine physiology ( J:227287 )

• intestinal permeability is high in tamoxifen treated mice

endocrine/exocrine glands

abnormal Paneth cell morphology ( J:227287 )

• unusually small in tumor-free mucosa of tamoxifen treated mice

hematopoietic system

increased CD103-positive CD11b-low dendritic cell number ( J:227287 )

• proportion of CD103+CD11b- dendritic cell subset involved in T-cell priming is higher in tamoxifen treated mice than in single conditional Apc heterozygous mice

increased CD8-positive, alpha-beta T cell number ( J:227287 )

• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice

• administration of IL-1beta receptor antagonist, anakinra, to tamoxifen treated mice is sufficient to prevent the expansion of cytotoxic CD8+ T cells

increased regulatory T cell number ( J:227287 )

• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice

immune system

increased CD103-positive CD11b-low dendritic cell number ( J:227287 )

• proportion of CD103+CD11b- dendritic cell subset involved in T-cell priming is higher in tamoxifen treated mice than in single conditional Apc heterozygous mice

increased CD8-positive, alpha-beta T cell number ( J:227287 )

• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice

• administration of IL-1beta receptor antagonist, anakinra, to tamoxifen treated mice is sufficient to prevent the expansion of cytotoxic CD8+ T cells

increased regulatory T cell number ( J:227287 )

• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice

abnormal immune system physiology ( J:227287 )

• tamoxifen treated mice show marked infiltration of lymphocytes within the normal mucosa, higher numbers of CD45 and T cells in the small intestine and colon mucosa, influx of CD11c+ cells in the intestinal mucosa compared to single conditional Apc heterozygous mice, indicating promotion of anti-tumor immune responses

increased interleukin-1 beta secretion ( J:227287 )

• immune cells isolated from the lamina propria of tamoxifen treated mice produce high amounts of IL-1beta

increased interleukin-10 secretion ( J:227287 )

• immune cells isolated from the lamina propria of tamoxifen treated mice produce high amounts of IL-10

cellular

abnormal intestinal goblet cell morphology ( J:227287 )

• abnormal accumulation of granules of mucus in goblet cells in the tumor-free mucosa of tamoxifen treated mice

Genotype
MGI:3829450

cn11

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

digestive/alimentary system

digestive/alimentary phenotype ( J:143082 )

N • following induction with tamoxifen in utero or in adult mice, crypt-villi architecture and physiology are normal

integument

ruffled hair ( J:143082 )

• when induced with tamoxifen in utero, mice develop a shaggy or ruffled coat

Genotype
MGI:5430368

cn12

• Allelic Composition: Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

digestive/alimentary system

abnormal small intestine goblet cell morphology ( J:185753 )

• 3 days after tamoxifen treatment, some goblet cells express Paneth cell markers

increased enterocyte apoptosis ( J:185753 )

• between day 1 and 5 of tamoxifen treatment

abnormal enterocyte proliferation ( J:185753 )

• tamoxifen-treated mice exhibit an absence of proliferative cells in the adult small intestine after 7 days of treatment

• cultured intestinal organoids treated with tamoxifen exhibit a block in proliferation and subsequent death of the organoid by day 6

abnormal intestine development ( J:185753 )

• 3 days after tamoxifen treatment, mice exhibit an elimination in Olfm4+ intestinal stem cells with the exception of in escaper crypts

decreased Paneth cell number ( J:185753 )

• 3 days after tamoxifen treatment, the small remaining Ki67+ escaper crypts contain limited numbers of correctly localized lysozyme-positive Paneth cells

absent Paneth cells ( J:185753 )

• 7 days after tamoxifen treatment, essentially all lysozyme-positive Paneth cells are eliminated

ectopic Paneth cells ( J:185753 )

• 3 days after tamoxifen treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi

cellular

abnormal small intestine goblet cell morphology ( J:185753 )

• 3 days after tamoxifen treatment, some goblet cells express Paneth cell markers

increased enterocyte apoptosis ( J:185753 )

• between day 1 and 5 of tamoxifen treatment

abnormal enterocyte proliferation ( J:185753 )

• tamoxifen-treated mice exhibit an absence of proliferative cells in the adult small intestine after 7 days of treatment

• cultured intestinal organoids treated with tamoxifen exhibit a block in proliferation and subsequent death of the organoid by day 6

endocrine/exocrine glands

decreased Paneth cell number ( J:185753 )

• 3 days after tamoxifen treatment, the small remaining Ki67+ escaper crypts contain limited numbers of correctly localized lysozyme-positive Paneth cells

absent Paneth cells ( J:185753 )

• 7 days after tamoxifen treatment, essentially all lysozyme-positive Paneth cells are eliminated

ectopic Paneth cells ( J:185753 )

• 3 days after tamoxifen treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi

Genotype
MGI:5430369

cn13

• Allelic Composition: Tcf7^tm1Cle/Tcf7^tm1Cle; Tcf7l1^tm1Efu/Tcf7l1^tm1Efu; Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

digestive/alimentary system

abnormal digestive system morphology ( J:185753 )

• tamoxifen-treatment results in the same defects as in Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice

abnormal digestive system physiology ( J:185753 )

• tamoxifen-treatment results in the same defects as in Tcf7l2^tm2.1Cle/Tcf7l2^tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice

Genotype
MGI:5438021

cn14

• Allelic Composition: Slc39a4^tm2Gka/Slc39a4^tm2Gka; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

Growth retardation of tamoxifen treated Slc39a4^tm2Gka/Slc39a4^tm2Gka Tg(Vil1-cre/ERT2)23Syr/0 mice

mortality/aging

lethality at weaning, complete penetrance ( J:187178 )

• mice treated with tamoxifen as neonates die within a week of weaning unless excess zinc is provided in the drinking water

premature death ( J:187178 )

• mice treated with tamoxifen (3 injections) 5 days after weaning die unless provided with excess zinc in the drinking water

• removal of excess zinc in the drinking water results in precipitous weight loss and death in mice treated with tamoxifen as neonates or after weaning

• excess zinc must be provided by day 6 after tamoxifen treatment to prevent lethality

• mice treated with tamoxifen at 7 weeks of age die around 1 week after the treatment

growth/size/body

weight loss ( J:187178 )

• rapid weight loss after weaning in mice treated with tamoxifen as neonates unless excess zinc is provided in the drinking water

• rapid weight loss is seen within a few days of tamoxifen treatment in mice treated with tamoxifen (3 injections) 5 days after weaning despite normal food consumption and much of this weight loss involves loss of muscle and bone

• mice given a single injection of tamoxifen after weaning slowly lose weight, about half recover and resume normal growth

• rapid weight loss is also seen when mice are treated with tamoxifen at 7 weeks of age

postnatal growth retardation ( J:187178 )

• mice treated with tamoxifen as neonates provided excess zinc in the drinking water at weaning still fail to gain much body weight following weaning

homeostasis/metabolism

abnormal mineral homeostasis ( J:187178 )

• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment

decreased intestinal iron level ( J:187178 )

• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment

abnormal copper level ( J:187178 )

• decrease in copper levels in the pancreas by 4 days after tamoxifen treatment

decreased intestine copper level ( J:187178 )

• by 4 days after tamoxifen treatment

• largest loss of copper occurs in the small intestine

decreased liver copper level ( J:187178 )

• by 4 days after tamoxifen treatment

increased liver copper level ( J:187178 )

• by 8 days after tamoxifen treatment

increased liver iron level ( J:187178 )

• levels are about twice normal by 8 days after tamoxifen treatment

abnormal zinc homeostasis ( J:187178 )

• decrease in zinc levels in the small intestine, pancreas and liver at 4 days after tamoxifen treatment

• decrease in zinc levels correlates with the beginning of weight loss

• levels in the liver normalize by 8 days after tamoxifen treatment

digestive/alimentary system

abnormal small intestinal crypt cell proliferation ( J:187178 )

• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment

decreased intestinal iron level ( J:187178 )

• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment

abnormal small intestine crypts of Lieberkuhn morphology ( J:187178 )

• progressive and profound disorganization of the crypt architecture after tamoxifen treatment

• crypts become elongated 2 days after tamoxifen treatment

abnormal Paneth cell morphology ( J:187178 )

• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted

abnormal small intestinal villus morphology ( J:187178 )

• progressive and profound disorganization of the villus after tamoxifen treatment

• by 6 days after tamoxifen treatment epithelial cells have lost much of their columnar morphology becoming cuboidal with centric nuclei

• by 6 days after tamoxifen treatment the lamina propria appears disorganized, occupies more space in the villi, and often contains red blood cells and cells with pyknotic nuclei

liver/biliary system

abnormal liver morphology ( J:187178 )

• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment

decreased liver copper level ( J:187178 )

• by 4 days after tamoxifen treatment

increased liver copper level ( J:187178 )

• by 8 days after tamoxifen treatment

increased liver iron level ( J:187178 )

• levels are about twice normal by 8 days after tamoxifen treatment

muscle

decreased muscle weight ( J:187178 )

• rapid muscle weight loss is seen within a few days of tamoxifen treatment in mice treated with tamoxifen 5 days after weaning despite normal food consumption

skeleton

decreased bone mass ( J:187178 )

• loss of bone mass is seen within a few days of tamoxifen treatment in mice treated with tamoxifen 5 days after weaning despite normal food consumption

cellular

abnormal small intestinal crypt cell proliferation ( J:187178 )

• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:187178 )

• progressive and profound disorganization of the crypt architecture after tamoxifen treatment

• crypts become elongated 2 days after tamoxifen treatment

abnormal Paneth cell morphology ( J:187178 )

• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrodermatitis enteropathica		DOID:0050605	OMIM:201100	J:187178

Genotype
MGI:3772216

cn15

• Allelic Composition: Pou5f1^tm1Scho/Pou5f1^tm1Scho; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:130248 )

N • mutants display normal intestinal tissue architecture, crypt regenerative capacity after irradiation, and normal weight gain

Genotype
MGI:5749127

cn16

• Allelic Composition: Vps35^tm1.1Hckn/Vps35^tm1.1Hckn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

4-hydroxytamoxifen treated Vps35^tm1.1Hckn/Vps35^tm1.1Hckn Tg(Vil1-cre/ERT2)23Syr/0 mice exhibit no differences in small intestine crypt or villus morphology

digestive/alimentary system

digestive/alimentary phenotype ( J:223191 )

N • at 3 days, 1 week, 4 weeks and 8 weeks after 4-hydroxytamoxifen (4-OHT) injection, adult mice exhibit no differences in crypt or villus morphology in the small intestine relative to control littermates

N • in culture, 4-OHT-treated small intestinal crypt organoids show reduced Wntless (Wls) protein levels but exhibit normal overall morphology, with Paneth cells visible at the tips of the bud, and can grow for many passages without Wnt supplementation in the growth medium

N • 4-OHT-treated intestinal organoids show normal survival rates in different R-spondin concentrations

abnormal small intestinal crypt cell proliferation ( J:223191 )

• 5 days after passaging, 4-OHT-treated intestinal organoids develop fewer crypt-like buds relative to control organoids, indicating a mild proliferation defect

• supplementation of exogenous Wnt3a in the medium does not fully rescue this growth defect, although 4-OHT-treated organoids can respond to Wnt signaling

cellular

abnormal small intestinal crypt cell proliferation ( J:223191 )

• 5 days after passaging, 4-OHT-treated intestinal organoids develop fewer crypt-like buds relative to control organoids, indicating a mild proliferation defect

• supplementation of exogenous Wnt3a in the medium does not fully rescue this growth defect, although 4-OHT-treated organoids can respond to Wnt signaling

Genotype
MGI:5702422

cn17

• Allelic Composition: Apc^tm2.1Cip/Apc^tm2.1Cip; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

premature death ( J:98469 )

• mice appear unwell and are moribund 4 days after tamoxifen injection

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:98469 )

• goblet cells are less numerous in the intestinal epithelium of tamoxifen treated mice

increased small intestinal crypt cell apoptosis ( J:98469 )

• tamoxifen treated mice show numerous apoptotic bodies in the crypts and higher number of apoptotic cells in the elongated crypts

abnormal intestine development ( J:98469 )

• marker analysis indicates that the intestinal mucosa of tamoxifen treated mice lacks differentiation into enterocytes, goblet, or enteroendocrine cells and is committed to the Paneth cell lineage, although most of the cells do not show typical granules indicating that they do not undergo full differentiation to the Paneth cell lineage

abnormal intestinal epithelium morphology ( J:98469 )

• tamoxifen treated mice exhibit an increase in cell proliferation in intestinal epithelium

• tamoxifen treated mice show slowed migration of epithelial cells along the crypt-villus axis in the epithelium

abnormal small intestine crypts of Lieberkuhn morphology ( J:98469 )

• tamoxifen treated mice show dysplasia in the crypt all along the small intestine, including pseudostratification, enlargement of the nuclei, prominent nucleoli, and basophil accumulation

• the crypt compartment of tamoxifen treated mice is greatly expanded

abnormal colon morphology ( J:98469 )

• tamoxifen treated mice show some rare lesions in the proximal colon which show characteristics similar to the small intestinal dysplasia

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:98469 )

• tamoxifen treated mice show dysplasia in the crypt all along the small intestine, including pseudostratification, enlargement of the nuclei, prominent nucleoli, and basophil accumulation

• the crypt compartment of tamoxifen treated mice is greatly expanded

cellular

abnormal intestinal goblet cell morphology ( J:98469 )

• goblet cells are less numerous in the intestinal epithelium of tamoxifen treated mice

increased small intestinal crypt cell apoptosis ( J:98469 )

• tamoxifen treated mice show numerous apoptotic bodies in the crypts and higher number of apoptotic cells in the elongated crypts

Genotype
MGI:5702414

cn18

• Allelic Composition: Apc^tm2.1Cip/Apc⁺; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

neoplasm

increased intestinal adenoma incidence ( J:227287 )

• tamoxifen treated mice develop intestinal adenomas after the sporadic loss of the remaining Apc allele

increased colon adenoma incidence ( J:227287 )

• tamoxifen treated mice develop colon adenomas after the sporadic loss of the remaining Apc allele

homeostasis/metabolism

abnormal autophagy ( J:227287 )

• tamoxifen-treated mice show activation of autophagy in tumoral cells

mortality/aging

decreased tumor-free survival time ( J:227287 )

• tamoxifen treated mice show signs of illness and have to be euthanized at 135 days due to large tumor burden

growth/size/body

cachexia ( J:227287 )

• tamoxifen treated mice show loss of body weight, pale feet and hunching

digestive/alimentary system

rectal prolapse ( J:227287 )

• tumors of tamoxifen treated mice in the distal colon and rectum are associated with frequent rectal prolapse

increased intestinal adenoma incidence ( J:227287 )

• tamoxifen treated mice develop intestinal adenomas after the sporadic loss of the remaining Apc allele

increased colon adenoma incidence ( J:227287 )

• tamoxifen treated mice develop colon adenomas after the sporadic loss of the remaining Apc allele

intestine polyps ( J:227287 )

• in tamoxifen treated mice

• prolonged antibiotic administration of tamoxifen treated mice does not affect severity of polyposis

• metaformin treatment impairs the growth of polyps in tamoxifen-treated mice but does not affect adenoma cell proliferation

abnormal gut flora balance ( J:227287 )

• tamoxifen treated mice show a difference in the overall composition of both fecal and ileal microbiota compared to double conditional mice heterozygous for Apc and homozygous for Atg7, with mice showing high levels of Gram- bacteria mostly from Helicobacter in the feces

• ileal mucosa of tamoxifen treated mice has a lower bacterial diversity than in double conditional mice heterozygous for Apc and homozygous for Atg7

• the ratio of Gram- to Gram+ bacteria is lower in tamoxifen treated mice than in double conditional mice heterozygous for Apc and homozygous for Atg7

cellular

abnormal autophagy ( J:227287 )

• tamoxifen-treated mice show activation of autophagy in tumoral cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:227287

Genotype
MGI:5581458

cn19

• Allelic Composition: Slc39a5^tm1Gka/Slc39a5^tm1Gka; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

homeostasis/metabolism

abnormal zinc homeostasis ( J:209760 )

• tamoxifen-treated mice provided adequate or excess zinc (by diet or gavage) exhibit increased pancreatic zinc compared with control mice

Genotype
MGI:3603010

cn20

• Allelic Composition: Rbpj^tm1Hon/Rbpj^tm1Hon; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:99348 )

• 6 days after the last injection of tamoxifen (given for 5 consecutive days), in the small intestine and colon the rapidly dividing transit amplifying compartment is replaced by post-mitotic goblet cells, with almost complete conversion by 12 days

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:99348 )

• 6 days after the last injection of tamoxifen (given for 5 consecutive days), in the small intestine and colon the rapidly dividing transit amplifying compartment is replaced by post-mitotic goblet cells, with almost complete conversion by 12 days

Genotype
MGI:5285825

cn21

• Allelic Composition: Lgr4^tm1.1Knis/Lgr4^tm1.1Knis; Lgr5^tm2.1Cle/Lgr5^tm2.1Cle; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

digestive/alimentary system

abnormal intestine physiology ( J:174842 )

• generated intestinal organoids degrade after 2 days of tamoxifen treatment

• however, organoid survival is rescued by retroviral expression of LGR5

Genotype
MGI:5568951

cn22

• Allelic Composition: Btrc^tm1Paga/Btrc^tm1Paga; Fbxw11^tm1Ybn/Fbxw11^tm1Ybn; Tg(Vil1-cre/ERT2)23Syr/?
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

rectal hemorrhage ( J:206654 )

• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours

diarrhea ( J:206654 )

• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours

abnormal enterocyte morphology ( J:206654 )

• wide gaps in epithelial tight junctions found in enterocytes following tamoxifen administration

abnormal intestinal mucosa morphology ( J:206654 )

• loss of most epithelial cells in large intestine following tamoxifen administration

• remaining mucosa is infiltrated with inflammatory and immune cells

• intestinal barrier disruption observed as early as 24 hours after tamoxifen treatment

abnormal large intestine crypts of Lieberkuhn morphology ( J:206654 )

• unrecognizable crypt structures in large intestine by day 5 following tamoxifen administration

abnormal colon morphology ( J:206654 )

• mice develop severe colitis following tamoxifen administration

• loss of most epithelial cells in large intestine following tamoxifen administration

• remaining mucosa is infiltrated with inflammatory and immune cells

intestinal inflammation ( J:206654 )

• inflammation in small and large intestines following tamoxifen administration

cellular

abnormal centrosome morphology ( J:206654 )

• more than 2 centrosomes observed in enterocytes following tamoxifen administration

abnormal mitosis ( J:206654 )

• mitosis is abnormally prolonged in enterocytes following tamoxifen administration

abnormal mitotic spindle morphology ( J:206654 )

• mitotic enterocytes have abnormal spindles following tamoxifen administration

chromosomal instability ( J:206654 )

• observed in enterocytes following tamoxifen administration

cardiovascular system

rectal hemorrhage ( J:206654 )

• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:206654 )

• unrecognizable crypt structures in large intestine by day 5 following tamoxifen administration

homeostasis/metabolism

increased circulating interleukin-1 beta level ( J:206654 )

• increase in IL1b levels beginning day 1 and spiking on day 3 following tamoxifen administration

immune system

intestinal inflammation ( J:206654 )

• inflammation in small and large intestines following tamoxifen administration

increased circulating interleukin-1 beta level ( J:206654 )

• increase in IL1b levels beginning day 1 and spiking on day 3 following tamoxifen administration

mortality/aging

premature death ( J:206654 )

• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours

Genotype
MGI:5568952

cn23

• Allelic Composition: Btrc^tm1Paga/Btrc⁺; Fbxw11^tm1Ybn/Fbxw11^tm1Ybn; Tg(Vil1-cre/ERT2)23Syr/?
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:206654 )

• severe inflammation and a disrupted epithelial layer occurs 4 days after tamoxifen administration

abnormal enterocyte morphology ( J:206654 )

• wide gaps in enterocyte epithelial tight junctions following tamoxifen administration

abnormal intestinal mucosa morphology ( J:206654 )

• mucositis observed in colon following tamoxifen administration

• spontaneous recovery occurs 3 weeks after tamoxifen administration

Genotype
MGI:6448987

cn24

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm3.1Tyj/Trp53^tm3.1Tyj
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

abnormal enterocyte morphology ( J:291671 )

• dysplastic in the colon and ileum, but not the duodenum and jejunum

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

Genotype
MGI:6448984

cn25

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm2.1Tyj/Trp53^tm2.1Tyj; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:291671 )

N • jejunal and ileal organoids exhibit normal organoid differentiation and proliferation

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

abnormal enterocyte morphology ( J:291671 )

• dysplastic in the colon and ileum, but not the duodenum and jejunum

• distal gut dysplasia appears earlier than in mice with null Trp53

• mice treated with gallic acid exhibit high-grade dysplastic foci unlike untreated mice\

• however, antibiotic treatment to eliminate gut bacteria results in shorter crypts and better organized villi

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

Genotype
MGI:6448985

cn26

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

endocrine/exocrine glands

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

Genotype
MGI:5902447

cn27

• Allelic Composition: Slc39a7^tm1.1Tfk/Slc39a7^tm1.1Tfk; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

premature death ( J:236234 )

• mice treated with tamoxifen for 5 days exhibit complete lethality by 7 days

• mice treated with tamoxifen for 3 days exhibit some lethality by day 4

• however, most mice survive at day 4 when treated with tamoxifen for 3 days

digestive/alimentary system

abnormal enterocyte physiology ( J:236234 )

• loss of epithelial integrity and stem cells in intestinal epithelial cells of tamoxifen-treated mice

increased enterocyte apoptosis ( J:236234 )

• of intestinal epithelial cells in tamoxifen-treated mice

abnormal enterocyte proliferation ( J:236234 )

• reduced proliferation of intestinal epithelial cells in tamoxifen-treated mice

cellular

increased enterocyte apoptosis ( J:236234 )

• of intestinal epithelial cells in tamoxifen-treated mice

abnormal enterocyte proliferation ( J:236234 )

• reduced proliferation of intestinal epithelial cells in tamoxifen-treated mice

Genotype
MGI:6448989

cn28

• Allelic Composition: Apc^Min/Apc⁺; Trp53^tm2.1Tyj/Trp53^tm2.1Tyj; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2

neoplasm

increased intestinal adenoma incidence ( J:291671 )

• as in Apc^Min heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract

increased colon adenoma incidence ( J:291671 )

• enhancement of tumorigenesis in the colon compared with Apc^Min heterozygotes

decreased alimentary system tumor incidence ( J:291671 )

• reduced tumor burden in the proximal gastrointestinal tract compared with Apc^Min heterozygotes

• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53

digestive/alimentary system

increased intestinal adenoma incidence ( J:291671 )

• as in Apc^Min heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract

increased colon adenoma incidence ( J:291671 )

• enhancement of tumorigenesis in the colon compared with Apc^Min heterozygotes

decreased alimentary system tumor incidence ( J:291671 )

• reduced tumor burden in the proximal gastrointestinal tract compared with Apc^Min heterozygotes

• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53

Genotype
MGI:5902497

cn29

• Allelic Composition: B3gnt6^tm1Lx/B3gnt6^tm1Lx; C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2

digestive/alimentary system

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• mice injected with tamoxifen at 1.5- to 4-months of age develop spontaneous duodenal tumors between 12 and 24 months of age, exhibiting mostly proliferative epithelium

increased duodenum adenocarcinoma incidence ( J:239765 )

• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma

neoplasm

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• mice injected with tamoxifen at 1.5- to 4-months of age develop spontaneous duodenal tumors between 12 and 24 months of age, exhibiting mostly proliferative epithelium

increased duodenum adenocarcinoma incidence ( J:239765 )

• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
duodenum cancer		DOID:10021		J:23965

Genotype
MGI:4888016

cn30

• Allelic Composition: Tle5^tm1.1Mmt/Tle5^tm1.1Mmt; Apc^tm1Mmt/Apc⁺; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA * SJL

neoplasm

increased colon adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased small intestine adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased metastatic potential ( J:168065 )

• treated with 4-hydroxytamoxifen to activate Cre recombinase at 3 weeks of age

• tumor invasion and intravasation into the smooth muscle layer of the small intestine and colon at 17 weeks of age

• in polyps larger than 2 mm in diameter, about half of them is found invading into the submucosa or beyond

• often seen inside vessels that are distended, reminiscent of tumor embolism

digestive/alimentary system

increased colon adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

increased small intestine adenocarcinoma incidence ( J:168065 )

• adenocarcinomas by histopathological definition

• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apc^tm1Mmt adenomas, without a very malignant appearance

Genotype
MGI:7310427

cn31

• Allelic Composition: Rpap3^{tm1c(KOMP)Wtsi}/Rpap3^{tm1c(KOMP)Wtsi}; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6N * DBA/2

digestive/alimentary system

abnormal small intestine morphology ( J:314346 )

• tamoxifen-treated mice exhibit a delay in epithelium shrinkage compared mice with at least one copy of wild-type Trp53

decreased small intestine length ( J:314346 )

• in tamoxifen-treated mice after 7 days

Genotype
MGI:3771553

cn32

• Allelic Composition: Slc40a1^tm2Nca/Slc40a1^tm2Nca; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA/2

hematopoietic system

anemia ( J:129846 )

• visibly anemic by 8 days after the first tamoxifen injection

• severe iron deficient anemia develops by 6 - 7 weeks after the start of tamoxifen treatment

decreased hematocrit ( J:129846 )

• by 6 - 7 weeks after the start of tamoxifen treatment, average hematocrit is 11.2 +/- 1.6% compared to 45.3 +/- 5.9% in controls without the cre transgene

• parenteral treatment with iron dextran restores hematocrits in tamoxifen treated mice to levels similar to control mice that do not carry the cre transgene

decreased hemoglobin content ( J:129846 )

• by 6 - 7 weeks after the start of tamoxifen treatment, average hemoglobin concentration is 2.8 +/- 0.6 g/dl compared to 13.8 +/- 1.8 g/dl in controls without the cre transgene

decreased spleen iron level ( J:129846 )

• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment

homeostasis/metabolism

increased intestinal iron level ( J:129846 )

• significant iron accumulation in duodenal enterocytes after tamoxifen treatment

decreased spleen iron level ( J:129846 )

• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment

decreased liver iron level ( J:129846 )

• a 5.5-fold decrease in hepatic nonheme iron is seen after tamoxifen treatment

digestive/alimentary system

increased intestinal iron level ( J:129846 )

• significant iron accumulation in duodenal enterocytes after tamoxifen treatment

immune system

decreased spleen iron level ( J:129846 )

• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment

liver/biliary system

decreased liver iron level ( J:129846 )

• a 5.5-fold decrease in hepatic nonheme iron is seen after tamoxifen treatment

Genotype
MGI:5689323

cn33

• Allelic Composition: Tfrc^tm3.1Nca/Tfrc^tm3.1Nca; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * DBA/2

mortality/aging

premature death ( J:224823 )

• mice are killed 1-3 days after the last tamoxifen dose due to poor health

• treatment with iron dextran does not extend lifespan in tamoxifen-treated mice

digestive/alimentary system

abnormal enterocyte proliferation ( J:224823 )

• reduced proliferation in tamoxifen-treated mice

diarrhea ( J:224823 )

• on the fourth day of tamoxifen treatment

blunted small intestinal villi ( J:224823 )

• blunted villi in tamoxifen-treated mice

distended stomach ( J:224823 )

• in tamoxifen-treated mice

growth/size/body

weight loss ( J:224823 )

• on the fourth day of tamoxifen treatment

cellular

abnormal enterocyte proliferation ( J:224823 )

• reduced proliferation in tamoxifen-treated mice

Genotype
MGI:5608788

cn34

• Allelic Composition: Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

cellular

abnormal small intestinal crypt cell proliferation ( J:215917 , J:278932 )

• adult mice administered tamoxifen exhibit increased crypt cell proliferation (J:215917)

• 2 days after tamoxifen administration, mice show a mild expansion of Olfm4+ crypt based columnar stem cells indicating entry of enterocytes into mitosis (J:278932)

digestive/alimentary system

abnormal small intestinal crypt cell proliferation ( J:215917 , J:278932 )

• adult mice administered tamoxifen exhibit increased crypt cell proliferation (J:215917)

• 2 days after tamoxifen administration, mice show a mild expansion of Olfm4+ crypt based columnar stem cells indicating entry of enterocytes into mitosis (J:278932)

immune system

increased interleukin-6 secretion ( J:215917 )

• intestinal organoid cultures induced with tamoxifen produce a 2-fold increase in interleukin-6 secretion

Genotype
MGI:5559518

cn35

• Allelic Composition: Xbp1^tm2Glm/Xbp1^tm2Glm; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

immune system

small intestinal inflammation ( J:206084 )

• treatment of mice with rapamycin reduces severity of enteritis

digestive/alimentary system

abnormal enterocyte physiology ( J:206084 )

• intenstinal epithelial cells exhibit ER (endoplamic reticulum) stress by 3 days after tamoxifen treatment

small intestinal inflammation ( J:206084 )

• treatment of mice with rapamycin reduces severity of enteritis

cellular

abnormal autophagy ( J:206084 )

• autophagy is induced in enterocytes, most notably in Paneth cells by 3 days after tamoxifen treatment

• treatment of mice with rapamycin induces autophagy in Paneth cells

homeostasis/metabolism

abnormal autophagy ( J:206084 )

• autophagy is induced in enterocytes, most notably in Paneth cells by 3 days after tamoxifen treatment

• treatment of mice with rapamycin induces autophagy in Paneth cells

Genotype
MGI:6721388

cn36

• Allelic Composition: Gt(ROSA)26Sor^{tm4(HIF2A*)Kael}/Gt(ROSA)26Sor^{tm4(HIF2A*)Kael}; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

digestive/alimentary system

increased susceptibility to colitis induced morbidity/mortality ( J:307422 )

• exacerbated dextran sodium sulfate (DSS)-induced colitis after induction of intestinal epithelium specific knockout with tamoxifen: significantly reduced colon length, severe tissue damage with massive loss of crypt architecture and inflammatory cell infiltrations

growth/size/body

growth/size/body region phenotype ( J:307422 )

N • no gross abnormalities; normal histology

immune system

increased susceptibility to colitis induced morbidity/mortality ( J:307422 )

• exacerbated dextran sodium sulfate (DSS)-induced colitis after induction of intestinal epithelium specific knockout with tamoxifen: significantly reduced colon length, severe tissue damage with massive loss of crypt architecture and inflammatory cell infiltrations

mortality/aging

mortality/aging ( J:307422 )

N • normal survival

increased susceptibility to colitis induced morbidity/mortality ( J:307422 )

• exacerbated dextran sodium sulfate (DSS)-induced colitis after induction of intestinal epithelium specific knockout with tamoxifen: significantly reduced colon length, severe tissue damage with massive loss of crypt architecture and inflammatory cell infiltrations

Genotype
MGI:5441534

cn37

• Allelic Composition: Xbp1^tm3Glm/Xbp1^tm3Glm; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

digestive/alimentary system

decreased Paneth cell number ( J:188627 )

• reduced numbers in tamoxifen-treated mice

decreased small intestinal villus size ( J:188627 )

• in tamoxifen-treated mice

abnormal intestine physiology ( J:188627 )

• increased apoptosis at the base of crypts (Paneth cells) and in villous epithelium (goblet cells) in tamoxifen-treated mice

small intestinal inflammation ( J:188627 )

• focal enteritis in 4 of 9 tamoxifen-treated mice ranges in severity from lamina propria polymorphpnuclear infiltration to crypt abscesses and ulceration without granulomas

• enteritis in 7 of 18 tamoxifen-treated mice

immune system

small intestinal inflammation ( J:188627 )

• focal enteritis in 4 of 9 tamoxifen-treated mice ranges in severity from lamina propria polymorphpnuclear infiltration to crypt abscesses and ulceration without granulomas

• enteritis in 7 of 18 tamoxifen-treated mice

cellular

increased apoptosis ( J:188627 )

• at the base of crypts (Paneth cells) and in villous epithelium (goblet cells) in tamoxifen-treated mice

endocrine/exocrine glands

decreased Paneth cell number ( J:188627 )

• reduced numbers in tamoxifen-treated mice

Genotype
MGI:5699005

cn38

• Allelic Composition: Numb^tm1Zili/Numb^tm1Zili; Tg(Vil1-cre/ERT2)23Syr/?
• Genetic Background: involves: 129/Sv * C57BL/6

homeostasis/metabolism

abnormal intestinal cholesterol absorption ( J:226578 )

• cholesterol endocytosis fails in tamoxifen treated mice

• less cholesterol absorption in liver

decreased circulating cholesterol level ( J:226578 )

• lower plasma cholesterol levels in tamoxifen treated mice

• partial resistance to diet induced hypercholesterolemia

digestive/alimentary system

abnormal intestinal cholesterol absorption ( J:226578 )

• cholesterol endocytosis fails in tamoxifen treated mice

• less cholesterol absorption in liver

Genotype
MGI:3721528

cn39

• Allelic Composition: Nr5a2^tm1Sjns/Nr5a2^tm1Sjns; Tg(Vil1-cre/ERT2)23Syr/?
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2 * SJL

digestive/alimentary system

colonic necrosis ( J:123697 )

• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis results in severe lesions with advanced necrosis

increased susceptibility to induced colitis ( J:123697 )

• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis is more severe than in wild-type mice

immune system

increased susceptibility to induced colitis ( J:123697 )

• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis is more severe than in wild-type mice

Genotype
MGI:4941917

cn40

• Allelic Composition: Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw; Cdc25b^tm1Pjd/Cdc25b^tm1Pjd; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

postnatal lethality, incomplete penetrance ( J:169457 )

• 2 of 5 tamoxifen-treated mice die by day 8

digestive/alimentary system

increased enterocyte apoptosis ( J:169457 )

• in tamoxifen-treated mice

abnormal enterocyte differentiation ( J:169457 )

• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice

abnormal small intestinal crypt cell proliferation ( J:169457 )

• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice

abnormal large intestine morphology ( J:169457 )

• reduced length in tamoxifen-treated mice

abnormal small intestine morphology ( J:169457 )

• reduced length in tamoxifen-treated mice

abnormal small intestine crypts of Lieberkuhn morphology ( J:169457 )

• tamoxifen treated mice exhibit a reduction in epithelium cells in the small intestine crypts compared with control mice

• however, the number of Paneth cells is normal

decreased small intestinal villus size ( J:169457 )

• in tamoxifen-treated mice

growth/size/body

decreased body weight ( J:169457 )

• in tamoxifen-treated mice

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:169457 )

• tamoxifen treated mice exhibit a reduction in epithelium cells in the small intestine crypts compared with control mice

• however, the number of Paneth cells is normal

cellular

increased enterocyte apoptosis ( J:169457 )

• in tamoxifen-treated mice

abnormal enterocyte differentiation ( J:169457 )

• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice

abnormal small intestinal crypt cell proliferation ( J:169457 )

• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice

Genotype
MGI:4941918

cn41

• Allelic Composition: Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw; Cdc25b^tm1Pjd/Cdc25b^tm1Pjd; Cdc25c^tm1Hpw/Cdc25c^tm1Hpw; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

postnatal lethality, incomplete penetrance ( J:169457 )

• 5 of 11 tamoxifen-treated mice die by day 8

digestive/alimentary system

increased enterocyte apoptosis ( J:169457 )

• in tamoxifen-treated mice

abnormal enterocyte differentiation ( J:169457 )

• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice

abnormal small intestinal crypt cell proliferation ( J:169457 )

• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice

abnormal large intestine morphology ( J:169457 )

• reduced length in tamoxifen-treated mice

abnormal small intestine morphology ( J:169457 )

• reduced length in tamoxifen-treated mice

abnormal small intestine crypts of Lieberkuhn morphology ( J:169457 )

• tamoxifen treated mice exhibit a reduction in epithelium cells in the small intestine crypts compared with control mice

• however, the number of Paneth cells is normal

decreased small intestinal villus size ( J:169457 )

• in tamoxifen-treated mice

growth/size/body

decreased body weight ( J:169457 )

• in tamoxifen-treated mice

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:169457 )

• tamoxifen treated mice exhibit a reduction in epithelium cells in the small intestine crypts compared with control mice

• however, the number of Paneth cells is normal

cellular

increased enterocyte apoptosis ( J:169457 )

• in tamoxifen-treated mice

abnormal enterocyte differentiation ( J:169457 )

• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice

abnormal small intestinal crypt cell proliferation ( J:169457 )

• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice

Genotype
MGI:4941915

cn42

• Allelic Composition: Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal large intestine morphology ( J:169457 )

• mild reduction in length in tamoxifen-treated mice

abnormal small intestine morphology ( J:169457 )

• mild reduction in length in tamoxifen-treated mice

growth/size/body

growth/size/body region phenotype ( J:169457 )

N • tamoxifen-treated mice exhibit normal body weight

Genotype
MGI:4941916

cn43

• Allelic Composition: Cdc25a^tm1Hpw/Cdc25a^tm1.1Hpw; Cdc25c^tm1Hpw/Cdc25c^tm1Hpw; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:169457 )

N • tamoxifen-treated mice exhibit normal intestine morphology

growth/size/body

growth/size/body region phenotype ( J:169457 )

N • tamoxifen-treated mice exhibit normal body weight

Genotype
MGI:4943329

cn44

• Allelic Composition: Cdc25b^tm1Hpw/Cdc25b^tm1Pjd; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:169457 )

N • tamoxifen-treated mice exhibit normal intestine morphology

growth/size/body

growth/size/body region phenotype ( J:169457 )

N • tamoxifen-treated mice exhibit normal body weight

Genotype
MGI:7545317

cn45

• Allelic Composition: Btnl1^em3Ahay/Btnl1^em3Ahay; Btnl6^em2Ahay/Btnl6^em2Ahay; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: BALB/c * C57BL/6J * DBA/2

immune system

immune system phenotype ( J:291989 )

N • after 8 weeks, tamoxifen-treated mice exhibit normal intraepithelial T cell numbers

Genotype
MGI:5512865

cn46

• Allelic Composition: Hprt1^{tm2(CAG-mCherry/Villin*)Syr}/?; Vil1^tm1Syr/Vil1^tm1Syr; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6

homeostasis/metabolism

impaired wound healing ( J:196199 )

• failure to heal properly at 3 and 7 days after carbachol treatment in tamoxifen induced mice

• very few cells in contact with sodium deoxycholate induced injury show polarity loss

Genotype
MGI:5512864

cn47

• Allelic Composition: Hprt1^{tm1(CAG-mCherry/Villin)Syr}/?; Vil1^tm1Syr/Vil1^tm1Syr; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:196199 )

N • after tamoxifen induction

N • injury repair after carbachol treatment is complete after 7 days as in control mice

N • columnar epithelium begins to flatten 30 minutes after injury with sodium deoxycholate

N • apico-basal polarity lost, microvillus disassembly

Genotype
MGI:5795900

cn48

• Allelic Composition: Tg(Vil1-cre/ERT2)23Syr/0; Zmiz1^{tm1c(EUCOMM)Hmgu}/Zmiz1^{tm1c(EUCOMM)Hmgu}
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA/2
• Cell Lines: HEPD0641_2_B09

digestive/alimentary system

digestive/alimentary phenotype ( J:234445 )

N • tamoxifen treated mice do not exhibit secretory hyperplasia and do not develop diarrhea or weight loss

Genotype
MGI:6721401

cn49

• Allelic Composition: Slc5a6^tm1.1Said/Slc5a6^tm1.1Said; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

digestive/alimentary system

intestinal hemorrhage ( J:307482 )

• bloody diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout

• no diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

diarrhea ( J:307482 )

• bloody diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout

• no diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

abnormal intestinal epithelium morphology ( J:307482 )

• significantly increased intestinal permeability after tamoxifen-induction of intestinal epithelium-specific knockout

abnormal large intestine crypts of Lieberkuhn morphology ( J:307482 )

• cryptitis and absence of crypts in cecum after tamoxifen-induction of intestinal epithelium-specific knockout

crypts of Lieberkuhn abscesses ( J:307482 )

• in cecum after tamoxifen-induction of intestinal epithelium-specific knockout

intestinal ulcer ( J:307482 )

• mucosal erosion in cecum after tamoxifen-induction of intestinal epithelium-specific knockout

decreased colon length ( J:307482 )

• after tamoxifen-induction of intestinal epithelium-specific knockout

• virtually normal colon length after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

abnormal intestinal epithelium physiology ( J:307482 )

• significantly increased intestinal permeability after tamoxifen-induction of intestinal epithelium-specific knockout

cecum inflammation ( J:307482 )

• severe chronic inflammation with cryptitis, crypt abscesses, and absence of crypts after tamoxifen-induction of intestinal epithelium-specific knockout

small intestinal inflammation ( J:307482 )

• acute inflammation with significant increase in neutrophil infiltration after tamoxifen-induction of intestinal epithelium-specific knockout

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:307482 )

• cryptitis and absence of crypts in cecum after tamoxifen-induction of intestinal epithelium-specific knockout

crypts of Lieberkuhn abscesses ( J:307482 )

• in cecum after tamoxifen-induction of intestinal epithelium-specific knockout

cardiovascular system

intestinal hemorrhage ( J:307482 )

• bloody diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout

• no diarrhea after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

growth/size/body

weight loss ( J:307482 )

• progressive decline in body weight after tamoxifen-induction of intestinal epithelium-specific knockout

• virtually normal weight after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

immune system

cecum inflammation ( J:307482 )

• severe chronic inflammation with cryptitis, crypt abscesses, and absence of crypts after tamoxifen-induction of intestinal epithelium-specific knockout

small intestinal inflammation ( J:307482 )

• acute inflammation with significant increase in neutrophil infiltration after tamoxifen-induction of intestinal epithelium-specific knockout

mortality/aging

premature death ( J:307482 )

• 50% of mice die within 8-10 days after tamoxifen-induction of intestinal epithelium-specific knockout

• normal 10-day survival after tamoxifen-induction of intestinal epithelium-specific knockout when administered broad-spectrum antibiotics

Genotype
MGI:6192735

cn50

• Allelic Composition: Lima1^tm1Blsg/Lima1⁺; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

digestive/alimentary system

decreased intestinal cholesterol absorption ( J:263730 )

homeostasis/metabolism

decreased intestinal cholesterol absorption ( J:263730 )

Genotype
MGI:6192734

cn51

• Allelic Composition: Lima1^tm1Blsg/Lima1^tm1Blsg; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:263730 )

N • plasma and liver triglyceride levels are normal when mice are fed a high-fat diet or regular chow

decreased intestinal cholesterol absorption ( J:263730 )

decreased circulating cholesterol level ( J:263730 )

• in mice fed a high-fat diet

decreased circulating HDL cholesterol level ( J:263730 )

• in mice fed a high-fat diet

decreased circulating LDL cholesterol level ( J:263730 )

• in mice fed a high-fat diet

decreased circulating VLDL cholesterol level ( J:263730 )

• in mice fed a high-fat diet

decreased liver cholesterol level ( J:263730 )

• in mice fed a high-fat diet

digestive/alimentary system

decreased intestinal cholesterol absorption ( J:263730 )

liver/biliary system

decreased liver cholesterol level ( J:263730 )

• in mice fed a high-fat diet

Genotype
MGI:5439367

cn52

• Allelic Composition: Rnf43^tm1Cle/Rnf43^tm1Cle; Znrf3^tm1Cle/Znrf3^tm1Cle; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

digestive/alimentary system

abnormal small intestinal crypt cell proliferation ( J:186765 )

• following tamoxifen treatment a marked expansion of the proliferative compartment is seen

abnormal small intestine crypts of Lieberkuhn morphology ( J:186765 )

• following tamoxifen treatment a marked expansion of the proliferative compartment is seen with enlarged crypts and Ki67+ cells ectopically located on the flanks of villi

• increase in the number of Olfm4+ stem cells after tamoxifen treatment

increased Paneth cell number ( J:186765 )

• increased number after tamoxifen treatment

increased intestinal adenoma incidence ( J:186765 )

• form within 1 month of clonal deletion induced by low dose tamoxifen treatment

• contain Olfm4+ stem cells and Paneth cells

neoplasm

increased intestinal adenoma incidence ( J:186765 )

• form within 1 month of clonal deletion induced by low dose tamoxifen treatment

• contain Olfm4+ stem cells and Paneth cells

cellular

abnormal small intestinal crypt cell proliferation ( J:186765 )

• following tamoxifen treatment a marked expansion of the proliferative compartment is seen

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:186765 )

• following tamoxifen treatment a marked expansion of the proliferative compartment is seen with enlarged crypts and Ki67+ cells ectopically located on the flanks of villi

• increase in the number of Olfm4+ stem cells after tamoxifen treatment

increased Paneth cell number ( J:186765 )

• increased number after tamoxifen treatment

Genotype
MGI:7545313

cn53

• Allelic Composition: Btnl1^em4Ahay/Btnl1^em4Ahay; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

immune system

immune system phenotype ( J:291989 )

N • for at least two weeks, tamoxifen-treated mice exhibit normal intraepithelial T cell numbers

Genotype
MGI:7310426

cn54

• Allelic Composition: Rpap3^{tm1c(KOMP)Wtsi}/Rpap3^{tm1c(KOMP)Wtsi}; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6N * DBA/2

digestive/alimentary system

abnormal enterocyte morphology ( J:314346 )

• disorganized with focal crowding in tamoxifen-treated mice after 7 days

abnormal small intestine morphology ( J:314346 )

• in tamoxifen-treated mice after 6 days

abnormal small intestine goblet cell morphology ( J:314346 )

• in tamoxifen-treated mice after 7 days

decreased small intestine length ( J:314346 )

• in tamoxifen-treated mice after 6 days

abnormal intestinal epithelium physiology ( J:314346 )

• tamoxifen-treated mice exhibit reduction in proliferating stem cells and progenitors and increased apoptosis compared with control mice

• however, differentiated Paneth cells are normal

small intestinal inflammation ( J:314346 )

• after 6 days, tamoxifen-treated mice exhibit massive intestinal swelling with a transparent liquid or blood compared with control mice

growth/size/body

weight loss ( J:314346 )

• in tamoxifen-treated mice after 6 days

immune system

small intestinal inflammation ( J:314346 )

• after 6 days, tamoxifen-treated mice exhibit massive intestinal swelling with a transparent liquid or blood compared with control mice

cellular

abnormal small intestine goblet cell morphology ( J:314346 )

• in tamoxifen-treated mice after 7 days

Genotype
MGI:6401286

tg55

• Allelic Composition: Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: C57BL/6 * DBA/2

digestive/alimentary system

abnormal intestinal epithelium physiology ( J:285672 )

• cultured crypts from tamoxifen-tested mice exhibit poor organoid growth compared with control cells

• crypts of tamoxifen-treated mice exhibit increased DNA damage from cloxP cleavage compared with control crypts

• however, mice exhibit normal enterocyte proliferation and apoptosis and restored regeneration after 7 days following irradiation

delayed intestine regeneration ( J:285672 )

• delayed intestine regeneration in tamoxifen-treated mice following challenge with 12 Gy irradiation

• however, mice not treated with tamoxifen exhibit normal response to irradiation

growth/size/body

increased susceptibility to weight loss ( J:285672 )

• increased weight loss in tamoxifen-treated mice following challenge with 12 Gy irradiation

• however, mice not treated with tamoxifen exhibit normal response to irradiation

homeostasis/metabolism

abnormal response to radiation ( J:285672 )

• following challenge with 12 Gy irradiation, tamoxifen-treated mice exhibit increased weight loss and intestinal damage with extensive decellularization of crypts, few crypt structures, and delayed regeneration compared with control mice

• however, mice not treated with tamoxifen exhibit normal response to irradiation