|
cn1
|
Tcf7l1tm1Efu/Tcf7l1tm1Efu Tg(Vil-cre/ERT2)23Syr/0 involves: 129 * C57BL/6 * DBA/2 |
|
|||||||||||||||||
| N |
• tamoxifen-treated mice exhibit normal adult intestinal homeostasis
(J:185753)
|
|
|
cn2
|
Tcf7tm1Cle/Tcf7tm1Cle Tcf7l1tm1Efu/Tcf7l1tm1Efu Tg(Vil-cre/ERT2)23Syr/0 involves: 129 * C57BL/6 * DBA/2 |
|
|||||||||||||||||
| N |
• tamoxifen-treated mice exhibit normal adult intestinal homeostasis
(J:185753)
|
|
|
cn3
|
Nr5a2tm1Sjns/Nr5a2tm1Sjns Tg(Vil-cre/ERT2)23Syr/? involves: 129/Sv * C57BL/6 * DBA/2 * SJL |
|
|||||||||||||||||
|
• 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
|
|
|
cn4
|
Ptentm2Mak/Ptentm2Mak Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * CBA |
|
|||||||||||||||||
| N |
• following induction with tamoxifen in utero or in adult mice, crypt-villi architecture and physiology are normal
(J:143082)
|
|
• when induced with tamoxifen in utero, mice develop a shaggy or ruffled coat
|
|
|
cn5
|
Rbpjtm1Hon/Rbpjtm1Hon Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• 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
|
|
• 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
|
|
|
cn6
|
Pou5f1tm1Scho/Pou5f1tm1Scho Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
| N |
• mutants display normal intestinal tissue architecture, crypt regenerative capacity after irradiation, and normal weight gain
(J:130248)
|
|
|
cn7
|
Lgr4tm1.1Knis/Lgr4tm1.1Knis Lgr5tm2.1Cle/Lgr5tm2.1Cle Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• generated intestinal organoids degrade after 2 days of tamoxifen treatment
• however, organoid survival is rescued by retroviral expression of LGR5
|
|
|
cn8
|
Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• between day 1 and 5 of tamoxifen treatment
|
|
• 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
|
|
• 3 days after tamoxifen-treatment, mice exhibit an elimination in Olfm4+ intestinal stem cells with the exception of in escaper crypts
|
|
• 1 day after tamoxifen-treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi
• 3 days after tamoxifen-treatment, some goblet cells express Paneth cell markers
|
|
• between day 1 and 5 of tamoxifen treatment
|
|
• 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
|
|
• 1 day after tamoxifen-treatment, Paneth cells are eliminated from the crypt of Lieberkuhn and aberrantly located on the villi
• 3 days after tamoxifen-treatment, some goblet cells express Paneth cell markers
|
|
|
cn9
|
Tcf7tm1Cle/Tcf7tm1Cle Tcf7l1tm1Efu/Tcf7l1tm1Efu Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• tamoxifen-treatment results in the same defects as in Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice
|
|
• tamoxifen-treatment results in the same defects as in Tcf7l2tm2.1Cle/Tcf7l2tm2.1Cle Tg(Vil-cre/ERT2)23Syr mice
|
|
|
cn10
|
Slc39a4tm2Gka/Slc39a4tm2Gka Tg(Vil-cre/ERT2)23Syr/0 involves: 129P2/OlaHsd * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• mice treated with tamoxifen as neonates die within a week of weaning unless excess zinc is provided in the drinking water
|
|
• 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
|
|
• 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
|
|
• mice treated with tamoxifen as neonates provided excess zinc in the drinking water at weaning still fail to gain much body weight following weaning
|
|
• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
|
|
• about a 50% decrease in copper levels in the small intestine by 4 days after tamoxifen treatment
|
|
• decrease in copper levels in the pancreas by 4 days after tamoxifen treatment
|
|
• by 4 days after tamoxifen treatment
• largest loss of copper occurs in the small intestine
|
|
• by 4 days after tamoxifen treatment
|
|
• by 8 days after tamoxifen treatment
|
|
• levels are about twice normal by 8 days after tamoxifen treatment
|
|
• 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
|
|
• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment
|
|
• 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
|
|
• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
|
|
• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted
|
|
• about a 50% decrease in copper levels in the small intestine by 4 days after tamoxifen treatment
|
|
• increase in manganese in the liver by 4 days after tamoxifen treatment with levels about twice normal by 8 days after treatment
|
|
• by 4 days after tamoxifen treatment
|
|
• by 8 days after tamoxifen treatment
|
|
• levels are about twice normal by 8 days after tamoxifen treatment
|
|
• 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
|
|
• 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
|
|
• decrease in proliferation at 2, 4 and 6 days after tamoxifen treatment
|
|
• progressive and profound disorganization of the crypt architecture after tamoxifen treatment
• crypts become elongated 2 days after tamoxifen treatment
|
|
• after tamoxifen treatment Paneth cells contain large cytoplasmic vacuoles and the store of labile zinc is rapidly depleted
|
Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Acrodermatitis Enteropathica, Zinc-Deficiency Type; AEZ | 201100 | J:187178 | |
|
|
cn11
|
Aestm1.1Mmt/Aestm1.1Mmt Apctm1Mmt/Apc+ Tg(Vil-cre/ERT2)23Syr/0 involves: 129S2/SvPas * C57BL/6 * DBA * SJL |
|
|||||||||||||||||
|
• 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
|
|
• 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
|
|
• 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
|
|
|
cn12
|
Slc40a1tm2Nca/Slc40a1tm2Nca Tg(Vil-cre/ERT2)23Syr/0 involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• 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
|
|
• 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
|
|
• 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
|
|
• 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
|
|
|
cn13
|
Cdc25atm1Hpw/Cdc25atm1.1Hpw Tg(Vil-cre/ERT2)23Syr/0 involves: 129X1/SvJ * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• mild reduction in length in tamoxifen-treated mice
|
|
• mild reduction in length in tamoxifen-treated mice
|
| N |
• tamoxifen-treated mice exhibit normal body weight
(J:169457)
|
|
|
cn14
|
Cdc25atm1Hpw/Cdc25atm1.1Hpw Cdc25ctm1Hpw/Cdc25ctm1Hpw Tg(Vil-cre/ERT2)23Syr/0 involves: 129X1/SvJ * C57BL/6 * DBA/2 |
|
|||||||||||||||||
| N |
• tamoxifen-treated mice exhibit normal intestine morphology
(J:169457)
|
| N |
• tamoxifen-treated mice exhibit normal body weight
(J:169457)
|
|
|
cn15
|
Cdc25atm1Hpw/Cdc25atm1.1Hpw Cdc25btm1Pjd/Cdc25btm1Pjd Tg(Vil-cre/ERT2)23Syr/0 involves: 129X1/SvJ * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• 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
|
|
• 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 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
|
|
|
cn16
|
Cdc25atm1Hpw/Cdc25atm1.1Hpw Cdc25btm1Pjd/Cdc25btm1Pjd Cdc25ctm1Hpw/Cdc25ctm1Hpw Tg(Vil-cre/ERT2)23Syr/0 involves: 129X1/SvJ * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• 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
|
|
• 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 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
|
|
|
cn17
|
Cdc25btm1Hpw/Cdc25btm1Pjd Tg(Vil-cre/ERT2)23Syr/0 involves: 129X1/SvJ * C57BL/6 * DBA/2 |
|
|||||||||||||||||
| N |
• tamoxifen-treated mice exhibit normal intestine morphology
(J:169457)
|
| N |
• tamoxifen-treated mice exhibit normal body weight
(J:169457)
|
|
|
cn18
|
Rnf43tm1Cle/Rnf43tm1Cle Znrf3tm1Cle/Znrf3tm1Cle Tg(Vil-cre/ERT2)23Syr/0 involves: C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• 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
|
|
• 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
|
|
|
cx19
|
Xbp1tm3Glm/Xbp1tm3Glm Tg(Vil-cre/ERT2)23Syr/0 involves: 129S6/SvEvTac * C57BL/6 * DBA/2 |
|
|||||||||||||||||
|
• in tamoxifen-treated mice
|
|
• reduced numbers 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
|