Analysis Tools
cellular
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• in the gut following tamoxifen treatment
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• in mouse embryonic fibroblasts following tamoxifen treatment
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Allele Symbol Allele Name Allele ID |
Tg(Vil1-cre/ERT2)23Syr transgene insertion 23, Sylvie Robine MGI:3053826 |
| Summary |
55 genotypes |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the gut following tamoxifen treatment
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• in mouse embryonic fibroblasts following tamoxifen treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice exhibit severe dysplasia and intramucosal carcinomas throughout the small bowel
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• massive proliferation in the villi compartment in tamoxifen-treated mice
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• massive proliferation in the villi compartment in tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 2 weeks of tamoxifen treatment
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• 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
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• increased proliferation after tamoxifen treatment throughout the crypt-villus axis
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• in the gut of tamoxifen treated mice but no more so than in Csnk1a1tm1.1Ybn/Csnk1a1tm1.1Ybn Tg(Vil-cre/ERT2)23Syr mice
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• increased proliferation after tamoxifen treatment throughout the crypt-villus axis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal adult intestinal homeostasis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal adult intestinal homeostasis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased proliferation in the entire bowel
• distal gut dysplasia appears later than in mice with Trp53tm2.1Tyj (containing the R172H missense mutation)
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• jejunal and ileal organoids exhibit increased proliferation, decreased differentiation, and resemble highly dysplastic spheroids
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• high-grade dysplasia in the entire bowel
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• enlarged and dysplastic
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• enlarged and dysplastic
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• increased proliferation in the entire bowel
• distal gut dysplasia appears later than in mice with Trp53tm2.1Tyj (containing the R172H missense mutation)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced number of intestinal tumors in duodenum and jejunum
• normal number of intestinal tumors in ileum and colon
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• reduced number of intestinal tumors in duodenum and jejunum
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• tumors less proliferative
• reduced ability to form colonies from single tumor cells in vitro
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• median intestinal tumor-free survival 138 vs 171 days
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• normal number of intestinal tumors in ileum and colon
• reduced number of intestinal tumors in duodenum and jejunum
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• reduced number of intestinal tumors in duodenum and jejunum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Microvillus inclusion disease phenotype in Myo5btm1.1Cle/Myo5btm1.1Cle Tg(Vil1-cre/ERT2)23Syr/0 mice
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• tamoxifen induced mice show intestinal crypt hyperplasia
• intercellular spaces between enterocytes are enlarged in tamoxifen induced mice
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• PAS-positive vesicles (secretory granules) are seen in crypt enterocytes and at the crypt-villus transition of tamoxifen treated mice
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• 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
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• intestines show a severe reduction to almost complete absence of apical microvilli on day 4 after tamoxifen induction
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• tamoxifen treated mice exhibit fusion of intestinal villi
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• mice show intestinal villus atrophy on day 4 after tamoxifen induction
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• mice exhibit severe weight loss starting from day 3 after tamoxifen induction
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• tamoxifen induced mice exhibit dehydration
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| microvillus inclusion disease | DOID:0060775 |
OMIM:251850 |
J:227079 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• abnormal accumulation of granules of mucus in goblet cells in the tumor-free mucosa of tamoxifen treated mice
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• unusually small in tumor-free mucosa of tamoxifen treated mice
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• 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
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• 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
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• intestinal permeability is high in tamoxifen treated mice
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• unusually small in tumor-free mucosa of tamoxifen treated mice
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• 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
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• 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
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• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice
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• 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
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• 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
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• the number of Treg and CD8 IFN-gamma T cells in the lamina propria is higher than in single conditional Apc heterozygous mice
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• 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
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• immune cells isolated from the lamina propria of tamoxifen treated mice produce high amounts of IL-1beta
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• immune cells isolated from the lamina propria of tamoxifen treated mice produce high amounts of IL-10
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• abnormal accumulation of granules of mucus in goblet cells in the tumor-free mucosa of tamoxifen treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following induction with tamoxifen in utero or in adult mice, crypt-villi architecture and physiology are normal
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• when induced with tamoxifen in utero, mice develop a shaggy or ruffled coat
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• generated intestinal organoids degrade after 2 days of tamoxifen treatment
• however, organoid survival is rescued by retroviral expression of LGR5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 3 days after tamoxifen treatment, some goblet cells express Paneth cell markers
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• between day 1 and 5 of tamoxifen treatment
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• 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
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• 3 days after tamoxifen treatment, mice exhibit an elimination in Olfm4+ intestinal stem cells with the exception of in escaper crypts
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• 3 days after tamoxifen treatment, the small remaining Ki67+ escaper crypts contain limited numbers of correctly localized lysozyme-positive Paneth cells
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• 7 days after tamoxifen treatment, essentially all lysozyme-positive Paneth cells are eliminated
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• 3 days after tamoxifen treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi
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• 3 days after tamoxifen treatment, some goblet cells express Paneth cell markers
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• between day 1 and 5 of tamoxifen treatment
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• 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
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• 3 days after tamoxifen treatment, the small remaining Ki67+ escaper crypts contain limited numbers of correctly localized lysozyme-positive Paneth cells
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• 7 days after tamoxifen treatment, essentially all lysozyme-positive Paneth cells are eliminated
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• 3 days after tamoxifen treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treatment results in the same defects as in Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice
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• tamoxifen-treatment results in the same defects as in Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice provided adequate or excess zinc (by diet or gavage) exhibit increased pancreatic zinc compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen treated mice develop intestinal adenomas after the sporadic loss of the remaining Apc allele
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• tamoxifen treated mice develop colon adenomas after the sporadic loss of the remaining Apc allele
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• tamoxifen-treated mice show activation of autophagy in tumoral cells
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• tamoxifen treated mice show signs of illness and have to be euthanized at 135 days due to large tumor burden
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• tumors of tamoxifen treated mice in the distal colon and rectum are associated with frequent rectal prolapse
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• 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
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• tamoxifen treated mice develop intestinal adenomas after the sporadic loss of the remaining Apc allele
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• tamoxifen treated mice develop colon adenomas after the sporadic loss of the remaining Apc allele
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• 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
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• tamoxifen-treated mice show activation of autophagy in tumoral cells
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:227287 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Growth retardation of tamoxifen treated Slc39a4tm2Gka/Slc39a4tm2Gka Tg(Vil1-cre/ERT2)23Syr/0 mice
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• mice treated with tamoxifen as neonates die within a week of weaning unless excess zinc is provided in the drinking water
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• 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
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• 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
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• mice treated with tamoxifen as neonates provided excess zinc in the drinking water at weaning still fail to gain much body weight following weaning
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• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
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• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment
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• decrease in copper levels in the pancreas by 4 days after tamoxifen treatment
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• by 4 days after tamoxifen treatment
• largest loss of copper occurs in the small intestine
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• by 4 days after tamoxifen treatment
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• by 8 days after tamoxifen treatment
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• levels are about twice normal by 8 days after tamoxifen treatment
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• 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
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• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment
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• about a 50% decrease in iron levels in the small intestine by 4 days after tamoxifen treatment
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• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
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• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted
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• 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
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• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
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• by 4 days after tamoxifen treatment
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• by 8 days after tamoxifen treatment
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• levels are about twice normal by 8 days after tamoxifen treatment
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• 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
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• 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
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• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment
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• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
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• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| acrodermatitis enteropathica | DOID:0050605 |
OMIM:201100 |
J:187178 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice appear unwell and are moribund 4 days after tamoxifen injection
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• goblet cells are less numerous in the intestinal epithelium of tamoxifen treated mice
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• tamoxifen treated mice show numerous apoptotic bodies in the crypts and higher number of apoptotic cells in the elongated crypts
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• 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
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• 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
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• 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
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• tamoxifen treated mice show some rare lesions in the proximal colon which show characteristics similar to the small intestinal dysplasia
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• 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
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• goblet cells are less numerous in the intestinal epithelium of tamoxifen treated mice
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• tamoxifen treated mice show numerous apoptotic bodies in the crypts and higher number of apoptotic cells in the elongated crypts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants display normal intestinal tissue architecture, crypt regenerative capacity after irradiation, and normal weight gain
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
4-hydroxytamoxifen treated Vps35tm1.1Hckn/Vps35tm1.1Hckn Tg(Vil1-cre/ERT2)23Syr/0 mice exhibit no differences in small intestine crypt or villus morphology
| 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
• 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
• 4-OHT-treated intestinal organoids show normal survival rates in different R-spondin concentrations
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severe inflammation and a disrupted epithelial layer occurs 4 days after tamoxifen administration
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• wide gaps in enterocyte epithelial tight junctions following tamoxifen administration
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• mucositis observed in colon following tamoxifen administration
• spontaneous recovery occurs 3 weeks after tamoxifen administration
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours
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• wide gaps in epithelial tight junctions found in enterocytes following tamoxifen administration
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• 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
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• unrecognizable crypt structures in large intestine by day 5 following tamoxifen administration
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• 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
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• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours
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• inflammation in small and large intestines following tamoxifen administration
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• more than 2 centrosomes observed in enterocytes following tamoxifen administration
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• mitosis is abnormally prolonged in enterocytes following tamoxifen administration
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• mitotic enterocytes have abnormal spindles following tamoxifen administration
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• observed in enterocytes following tamoxifen administration
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• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours
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• unrecognizable crypt structures in large intestine by day 5 following tamoxifen administration
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• increase in IL1b levels beginning day 1 and spiking on day 3 following tamoxifen administration
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• inflammation in small and large intestines following tamoxifen administration
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• increase in IL1b levels beginning day 1 and spiking on day 3 following tamoxifen administration
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• appearance of severe diarrhea and rectal bleeding in mice given tamoxifen is followed by death within 24 hours
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased proliferation in the colon and ileum, but not the duodenum and jejunum
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• dysplastic in the colon and ileum, but not the duodenum and jejunum
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• increased proliferation in the colon and ileum, but not the duodenum and jejunum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• jejunal and ileal organoids exhibit normal organoid differentiation and proliferation
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• 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
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• enlarged and dysplastic
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• enlarged and dysplastic
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• loss of epithelial integrity and stem cells in intestinal epithelial cells of tamoxifen-treated mice
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• of intestinal epithelial cells in tamoxifen-treated mice
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• reduced proliferation of intestinal epithelial cells in tamoxifen-treated mice
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• of intestinal epithelial cells in tamoxifen-treated mice
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• reduced proliferation of intestinal epithelial cells in tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced tumor burden in the proximal gastrointestinal tract compared with ApcMin heterozygotes
• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53
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• as in ApcMin heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract
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• enhancement of tumorigenesis in the colon compared with ApcMin heterozygotes
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• reduced tumor burden in the proximal gastrointestinal tract compared with ApcMin heterozygotes
• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53
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• as in ApcMin heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract
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• enhancement of tumorigenesis in the colon compared with ApcMin heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma
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• 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
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• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| duodenum cancer | DOID:10021 | J:23965 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adenocarcinomas by histopathological definition
• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apctm1Mmt adenomas, without a very malignant appearance
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• adenocarcinomas by histopathological definition
• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apctm1Mmt adenomas, without a very malignant appearance
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• 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
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• adenocarcinomas by histopathological definition
• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apctm1Mmt adenomas, without a very malignant appearance
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• adenocarcinomas by histopathological definition
• the extent of cellular atypia and epithelial architecture are rather similar to those in the Apctm1Mmt adenomas, without a very malignant appearance
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice exhibit a delay in epithelium shrinkage compared mice with at least one copy of wild-type Trp53
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• in tamoxifen-treated mice after 7 days
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 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
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• 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
|
|
• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment
|
|
• significant iron accumulation in duodenal enterocytes after tamoxifen treatment
|
|
• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment
|
|
• a 5.5-fold decrease in hepatic nonheme iron is seen after tamoxifen treatment
|
|
• significant iron accumulation in duodenal enterocytes after tamoxifen treatment
|
|
• a 4.7-fold decrease in splenic nonheme iron is seen after tamoxifen treatment
|
|
• a 5.5-fold decrease in hepatic nonheme iron is seen after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• reduced proliferation in tamoxifen-treated mice
|
|
• blunted villi in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• on the fourth day of tamoxifen treatment
|
|
• reduced proliferation in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
| N |
• no gross abnormalities; normal histology
|
|
• 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
|
| N |
• normal survival
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced numbers in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• increased apoptosis at the base of crypts (Paneth cells) and in villous epithelium (goblet cells) in tamoxifen-treated mice
|
|
• 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
|
|
• 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
|
|
• at the base of crypts (Paneth cells) and in villous epithelium (goblet cells) in tamoxifen-treated mice
|
|
• reduced numbers in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adult mice administered tamoxifen exhibit increased crypt cell proliferation
|
|
• adult mice administered tamoxifen exhibit increased crypt cell proliferation
|
|
• intestinal organoid cultures induced with tamoxifen produce a 2-fold increase in interleukin-6 secretion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• treatment of mice with rapamycin reduces severity of enteritis
|
|
• intenstinal epithelial cells exhibit ER (endoplamic reticulum) stress by 3 days after tamoxifen treatment
|
|
• treatment of mice with rapamycin reduces severity of enteritis
|
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cholesterol endocytosis fails in tamoxifen treated mice
• less cholesterol absorption in liver
|
|
• lower plasma cholesterol levels in tamoxifen treated mice
• partial resistance to diet induced hypercholesterolemia
|
|
• cholesterol endocytosis fails in tamoxifen treated mice
• less cholesterol absorption in liver
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis results in severe lesions with advanced necrosis
|
|
• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis is more severe than in wild-type mice
|
|
• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis is more severe than in wild-type mice
|
|
• following treatment with tamoxifen, 2,4,6-trinitrobezene sulfonic acid (TNBS)-induced colitis results in severe lesions with advanced necrosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 of 11 tamoxifen-treated mice die by day 8
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice
|
|
• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice
|
|
• reduced length in tamoxifen-treated mice
|
|
• reduced length in tamoxifen-treated mice
|
|
• 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
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• 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
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice
|
|
• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal intestine morphology
|
| N |
• tamoxifen-treated mice exhibit normal body weight
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 of 5 tamoxifen-treated mice die by day 8
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice
|
|
• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice
|
|
• reduced length in tamoxifen-treated mice
|
|
• reduced length in tamoxifen-treated mice
|
|
• 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
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• 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
|
|
• in tamoxifen-treated mice
|
|
• tamoxifen-treated mice exhibit premature differentiation of small intestine crypt cells compared with control mice
|
|
• tamoxifen-treated mice exhibit decreased S-phase cells in crypts compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mild reduction in length in tamoxifen-treated mice
|
|
• mild reduction in length in tamoxifen-treated mice
|
| N |
• tamoxifen-treated mice exhibit normal body weight
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal intestine morphology
|
| N |
• tamoxifen-treated mice exhibit normal body weight
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• after tamoxifen induction
• injury repair after carbachol treatment is complete after 7 days as in control mice
• columnar epithelium begins to flatten 30 minutes after injury with sodium deoxycholate
• apico-basal polarity lost, microvillus disassembly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen treated mice do not exhibit secretory hyperplasia and do not develop diarrhea or weight loss
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tamoxifen treatment a marked expansion of the proliferative compartment is seen
|
|
• 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 number after tamoxifen treatment
|
|
• form within 1 month of clonal deletion induced by low dose tamoxifen treatment
• contain Olfm4+ stem cells and Paneth cells
|
|
• form within 1 month of clonal deletion induced by low dose tamoxifen treatment
• contain Olfm4+ stem cells and Paneth cells
|
|
• following tamoxifen treatment a marked expansion of the proliferative compartment is seen
|
|
• 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 number after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• significantly increased intestinal permeability after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• cryptitis and absence of crypts in cecum after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• in cecum after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• mucosal erosion in cecum after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• 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
|
|
• 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
|
|
• significantly increased intestinal permeability after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• severe chronic inflammation with cryptitis, crypt abscesses, and absence of crypts after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• acute inflammation with significant increase in neutrophil infiltration after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• cryptitis and absence of crypts in cecum after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• in cecum after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• 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
|
|
• 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
|
|
• severe chronic inflammation with cryptitis, crypt abscesses, and absence of crypts after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• acute inflammation with significant increase in neutrophil infiltration after tamoxifen-induction of intestinal epithelium-specific knockout
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• plasma and liver triglyceride levels are normal when mice are fed a high-fat diet or regular chow
|
|
• in mice fed a high-fat diet
|
|
• in mice fed a high-fat diet
|
|
• in mice fed a high-fat diet
|
|
• in mice fed a high-fat diet
|
|
• in mice fed a high-fat diet
|
|
• in mice fed a high-fat diet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• for at least two weeks, tamoxifen-treated mice exhibit normal intraepithelial T cell numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• after 8 weeks, tamoxifen-treated mice exhibit normal intraepithelial T cell numbers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disorganized with focal crowding in tamoxifen-treated mice after 7 days
|
|
• in tamoxifen-treated mice after 6 days
|
|
• in tamoxifen-treated mice after 7 days
|
|
• in tamoxifen-treated mice after 6 days
|
|
• tamoxifen-treated mice exhibit reduction in proliferating stem cells and progenitors and increased apoptosis compared with control mice
• however, differentiated Paneth cells are normal
|
|
• after 6 days, tamoxifen-treated mice exhibit massive intestinal swelling with a transparent liquid or blood compared with control mice
|
|
• in tamoxifen-treated mice after 6 days
|
|
• after 6 days, tamoxifen-treated mice exhibit massive intestinal swelling with a transparent liquid or blood compared with control mice
|
|
• in tamoxifen-treated mice after 7 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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 in tamoxifen-treated mice following challenge with 12 Gy irradiation
• however, mice not treated with tamoxifen exhibit normal response to irradiation
|
|
• increased weight loss in tamoxifen-treated mice following challenge with 12 Gy irradiation
• however, mice not treated with tamoxifen exhibit normal response to irradiation
|
|
• 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
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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