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Allele Symbol Allele Name Allele ID |
Lgr5tm1(cre/ERT2)Cle targeted mutation 1, Hans Clevers MGI:3764660 |
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| Summary |
26 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal intestinal morphology and physiology under basal conditions and normal response to irradiation
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• intestinal stem cells treated with tamoxifen exhibit impaired organoid formation compared with control cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• form after tamoxifen treatment and contain Olfm4+ stem cells and Paneth cells
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• form after tamoxifen treatment and contain Olfm4+ stem cells and Paneth cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all tamoxifen-treated mice die within 4 days of gamma irradiation
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| N |
• tamoxifen-treated mice exhibit normal epithelial organoid and crypt-derived epithelial organoid formation
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• tamoxifen-treated mice exhibit massive apoptosis of transit-amplifying cells due to increased ER stress
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• degeneration of Paneth cells in tamoxifen-treated mice
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• all tamoxifen-treated mice die within 4 days of gamma irradiation
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• degeneration of Paneth cells in tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in tamoxifen-treated mice compared with Apctm1Tno/Apctm1Tno Lgr5tm1(cre/ERT2)Cle/Lgr5+ mice
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• tamoxifen-treated mice exhibit a reduced total tumor burden and average tumor size of abnormally proliferating adenomas in the small intestine and reduced size, but not number, of colon adenomas due to reduced proliferation and increased reactive oxygen species damage compared with Apctm1Tno/Apctm1Tno Lgr5tm1(cre/ERT2)Cle/Lgr5+ mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen treated mice develop numerous hyperplasias in the intestine
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• tamoxifen treated mice develop numerous hyperplasias in the intestine
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the amount of Dclk1+/Sox9+ cells in the Lgr5+ population is decreased in ex vivo organoids
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• intestinal crypts fail to efficiently generate spheroid structures ex vivo
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• tamoxifen treated mice exhibit decreased numbers of hyperplastic foci/polyps in the intestine indicating impaired tumor initiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lyzsozyme+ Paneth cells in doxycycline-treated mice are not restricted to the base of the crypt unlike in control cells
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• expanded crypts in the ileum of doxycycline-treated mice
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• increased cell proliferation in the intestine of doxycycline-treated mice with an increase in intestinal stem Lgr5+ cells
• increased proliferation of intestinal stem cells in the intestine of doxycycline-treated mice
• expansion of intestinal stem cells is cell autonomous in doxycycline treated mice
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• in the intestine of doxycycline-treated mice with an increase in Lgr5+ intestinal stem cells
• increased proliferation of intestinal stem cells in the intestine of doxycycline-treated mice
• expansion of intestinal stem cells is cell autonomous in doxycycline treated mice
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• lyzsozyme+ Paneth cells in doxycycline-treated mice are not restricted to the base of the crypt unlike in control cells
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• expanded crypts in the ileum of doxycycline-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• expanded crypts in the ileum of doxycycline-treated mice
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• increased cell proliferation in the intestine of doxycycline-treated mice without an increase in Lgr5+ cells
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• in the intestine of doxycycline-treated mice without an increase in Lgr5+ cells
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• expanded crypts in the ileum of doxycycline-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• impaired intestinal epithelial renewal in tamoxifen treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced cycling and proliferation of intestinal stem cells
• however, proliferation rates are normal
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• reduced cycling and proliferation of intestinal stem cells
• however, proliferation rates are normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• authors state that tamoxifen-treated mice exhibit similar phenotype as Nrbp1tm1.1Dja/Nrbp1tm1.1Dja Gt(ROSA)26Sortm1(cre/ERT)Brn/ Gt(ROSA)26Sor+ mice
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• abnormal goblet cell production in tamoxifen-treated mice
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• abnormal granularization of Paneth cells in tamoxifen-treated mice
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• abnormal localization of Paneth cells in tamoxifen-treated mice
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• abnormal granularization of Paneth cells in tamoxifen-treated mice
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• abnormal localization of Paneth cells in tamoxifen-treated mice
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• abnormal goblet cell production in tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in proliferation of intestinal epithelial stem cells and the transit-amplifying cells following tamoxifen induction
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 40 days after tamoxifen treatment, mice have developed numerous polyps
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• intestinal crypt stem cells show increased cell death following tamoxifen administration
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• 3 weeks after tamoxifen administration, mutant villus epithelial cells show disrupted cell polarity, as indicated by disorganized nuclear alignment
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration
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• 3 weeks after tamoxifen administration, more mutant stem cells in intestinal crypts undergo mitosis compared to control stem cells
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration, indicating reduced clonal expansion of mutant stem cells
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• 2 weeks after tamoxifen administration, mutant stem cells in intestinal crypts fail to give rise to Paneth cells
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• 3 weeks after tamoxifen administration, mutant villus epithelial cells show disrupted cell polarity, as indicated by disorganized nuclear alignment
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• 3 weeks after tamoxifen administration, more mutant stem cells in intestinal crypts undergo mitosis compared to control stem cells
• stem cells contribute less to the villus epithelial compartments than in controls following tamoxifen administration, indicating reduced clonal expansion of mutant stem cells
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• 2 weeks after tamoxifen administration, mutant stem cells in intestinal crypts fail to give rise to Paneth cells
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• intestinal crypt stem cells show increased cell death following tamoxifen administration
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• one week after tamoxifen administration, 56% of mutant crypts show stem cells forming a clustering pattern lacking clear demarcation between each other, while at 3 weeks after tamoxifen administration, 85% do so
• stem cells in mutant crypts 3 weeks after tamoxifen treatment lose the typical triangle shapes and marker analysis indicates disrupted crypt cell polarity
• loss of stem cells
• intestinal crypt cells, most likely Paneth cells, contain large vacuoles
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• reduction or absence of Paneth cell granules, indicating loss of Paneth cells
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• one week after tamoxifen administration, 56% of mutant crypts show stem cells forming a clustering pattern lacking clear demarcation between each other, while at 3 weeks after tamoxifen administration, 85% do so
• stem cells in mutant crypts 3 weeks after tamoxifen treatment lose the typical triangle shapes and marker analysis indicates disrupted crypt cell polarity
• loss of stem cells
• intestinal crypt cells, most likely Paneth cells, contain large vacuoles
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• reduction or absence of Paneth cell granules, indicating loss of Paneth cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced intestinal stem cells with impaired organoid formation capacity
• however, overexpression of Ehf rescues this phenotype
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• short with fewer cells than in wild-type mice
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• short with fewer cells than in wild-type mice
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• impaired intestinal epithelium regeneration after radiation injury compared with wild-type mice
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• short with fewer cells than in wild-type mice
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• impaired intestinal epithelium regeneration after radiation injury compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced proliferation of intestinal stem cells after 5-fluoruracil (5-FU)-induced killing of proliferating intestinal cells
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• reduced proliferation of intestinal stem cells after 5-fluoruracil (5-FU)-induced killing of proliferating intestinal cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced intestinal stem cells with impaired organoid formation capacity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• almost blocked organoid formation from intestinal stem cells
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• severely impaired intestinal epithelium regeneration after radiation injury compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 6 weeks after treatment cystic vesicles persist and are often filled with mucous and detritus
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• an excess of Paneth cells are found by 19-62 weeks after treatment and these cells contain an abnormally abundant number of normal looking secretory granules
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• 4 weeks after treatment with tamoxifen a low level of excess mucous secretion is seen
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• by 6 weeks after treatment dying Paneth cells are commonly seen
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• recombined cells fail to migrate out of the crypts and up the villi in the intestine
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• by 6 weeks after treatment cystic vesicles persist and are often filled with mucous and detritus
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• an excess of Paneth cells are found by 19-62 weeks after treatment and these cells contain an abnormally abundant number of normal looking secretory granules
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen treated mice show normal numbers of Lgr5+ cells in intestinal crypts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased Lgr5-GFP+ cells pre and post tamoxifen treatment
• tamoxifen-treated cultured intestinal crypt organoids exhibit fewer outgrowths and fail to reform after disaggregation unlike control cultures
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen-treated mice are normal and survive for 3 weeks at least
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 5-6 months, nearly 90% of mice develop duodenal tumors (usually low grade adenomas)
• in one instance, a 13-month old mouse had a tumor with areas showing high grade dysplasia, and focal extension of neoplastic glands into deeper layers of the bowel wall; tumor showed intact Apc however
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• number of crypts showing Lgr5-EGFP fluorescence is doubled in absence of Lrig1 protein, compared to mice with one or two copies of Lrig1
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• at 5-6 months, nearly 90% of mice develop duodenal tumors (usually low grade adenomas)
• in one instance, a 13-month old mouse had a tumor with areas showing high grade dysplasia, and focal extension of neoplastic glands into deeper layers of the bowel wall; tumor showed intact Apc however
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• number of crypts showing Lgr5-EGFP fluorescence is doubled in absence of Lrig1 protein, compared to mice with one or two copies of Lrig1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 16% of mice exhibit postnatal lethality associated with disturbances in the intestinal epithelium
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• disturbances in the intestinal epithelium
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• loss of Lgr5+ intestinal stem cells in the intestine
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• loss of Lgr5+ intestinal stem cells in the intestine
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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 04/23/2024 MGI 6.23 |
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