growth/size/body
• reduced body weight at E17.5 - E18.5 compared to wild-type mice, but mice are heavier than homozygotes
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Allele Symbol Allele Name Allele ID |
Polr2a+ wild type MGI:2435433 |
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Summary |
13 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• reduced body weight at E17.5 - E18.5 compared to wild-type mice, but mice are heavier than homozygotes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 2 weeks after 5-hydroxytamoxifen treatment, lungs show increased cellularity
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• lungs show multicellular septa and reduction of the alveolar lumen as early as 2 weeks after 5-hydroxytamoxifen treatment, and is marked after 8 weeks, extending to 60% of the lungs
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• after 5-hydroxytamoxifen treatment, there is an increase in alveolar type II cells compared to controls
• when cultured, isolated progenitor and stem cells (SP-C+, CC-10+ cells) when put under differentiation conditions do not have the capacity to form single positive cells; overexpression of C/EBP alpha in these cells restores the capacity to form SP-C+ cells
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• 8 weeks after 5-hydroxytamoxifen treatment, lungs display hyperproliferation (~5-fold increased proliferation) compared to wild-type or heterozygous lungs
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
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• with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• when cells are exposed to tamoxifen ex vivo, the progenitor compartment is increased compared to unexposed cells
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• when cells are exposed to tamoxifen ex vivo, the number of myeloid colony forming units is increased compared to unexposed cells
• when cells are exposed to tamoxifen ex vivo, the proliferation of myeloid precursor cells is increased compared to unexposed cells
• however, myeloid cell apoptosis rates and differentiation are normal
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• when cells are exposed to tamoxifen ex vivo, fewer pre-B cells are present compared to unexposed cells
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• when cells are exposed to tamoxifen ex vivo, fewer pre-B cells are present compared to unexposed cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice live up to 40 weeks
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• by 24 weeks, mice develop tumors in the thymus
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• by 24 weeks, mice develop tumors in lungs
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• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals
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• by 24 weeks, mice develop tumors in lungs
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• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice die before week 32 due to increased lung cancer progression
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• 20 weeks after treatment, lungs are increased in size
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• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
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• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
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• adenocarcinomas are detected at 15 weeks but not in controls
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• lung differentiation is abnormal with increased SP-C-positive cells
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• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus
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• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
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• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
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• adenocarcinomas are detected at 15 weeks but not in controls
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• 20 weeks after treatment, lungs are increased in size
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice die before week 32 due to increased lung cancer progression
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• 20 weeks after treatment, lungs are increased in size
|
• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
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• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
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• adenocarcinomas are detected at 15 weeks but not in controls
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• lung differentiation is abnormal with increased SP-C-positive cells
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• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus
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• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
|
• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
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• adenocarcinomas are detected at 15 weeks but not in controls
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• 20 weeks after treatment, lungs are increased in size
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• after topical application of 4-hydroxytamoxifen
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• topical application of 4-hydroxytamoxifen to the unshaved tail results in complete alopecia by 6 weeks after application
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• fewer hair follicle bulges are detected 4 - 6 weeks after topical application of 4-hydroxytamoxifen
• at 2 - 3 weeks after topical application of 4-hydroxytamoxifen the long term retaining cell region is expanded but by 6 weeks after application long term retaining cells appear to be lost
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• broad disorganization of the interfollicular epithelium develops by 3 - 4 weeks after topical application of 4-hydroxytamoxifen
• hyperkeratosis is associated with loss of cellularity in the interfollicular epithelium
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• develops by 3 - 4 weeks after topical application of 4-hydroxytamoxifen
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• after topical application of 4-hydroxytamoxifen
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• after topical application of 4-hydroxytamoxifen
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• massive hyperplasia with increased cellularity in the interfollicular epithelium and the infundibulum in the first few weeks after topical application of 4-hydroxytamoxifen
• no abnormal cell death is seen in these lesions
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• by 2 - 4 weeks after topical application of 4-hydroxytamoxifen, severe skin ulcerative lesions develop
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• between 1 - 2 weeks after topical application of 4-hydroxytamoxifen, back skin is ruffled and wrinkled
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• between 1 - 2 weeks after topical application of 4-hydroxytamoxifen, back skin is thickened
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• increase in the proportion of proliferating epidermal cells in the first few weeks after topical application of 4-hydroxytamoxifen
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• after 10 - 15 days in culture keratinocytes from 4-hydroxytamoxifen treated skin fail to develop typical holoclones (corresponding to long term clonal outgrowth of epidermal stem cells)
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• development of hyperkeratosis following 4-hydroxytamoxifen treatment is reduced and delayed compared to mutant mice wild-type for Cdkn2a
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• development of hyperplasia following 4-hydroxytamoxifen treatment is reduced and delayed compared to mutant mice wild-type for Cdkn2a
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• partial restoration in long term outgrowth of 4-hydroxytamoxifen exposed keratinocytes in culture compared to mutant mice wild-type for Cdkn2a
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• after 8 to 10 days on a tamoxifen diet
• however, survival is increased when older mice (1 year old) are treated with tamoxifen
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• tamoxifen-treated mice exhibit widespread metaphase arrest in proliferative areas of the intestine and testis unlike in control mice
• topical treatment results in metaphase figures in the basal layer and in the hair follicle cells in depilated mice compared to in similarly treated control mice
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• tamoxifen-treated mice exhibit reduced proliferation in the testis and spleen compared with control mice
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• in a two-stage carcinogenesis protocol, tamoxifen-treated mice exhibit tumor arrest unlike similarly treated control mice
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• in tamoxifen-treated mice
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• following topical application of tamoxifen, depilated mice exhibit impaired hair regeneration compared with similarly treated control mice
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• topical treatment results in metaphase figures in the basal layer compared to in similarly treated control mice
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• tamoxifen-treated mice exhibit loss of intestinal epithelium unlike in control mice
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• in tamoxifen-treated mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• fewer CD25-kappa+ immature B cells in tamoxifen-treated mice
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• fewer CD25+kappa- pre-B cells in tamoxifen-treated mice
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• fewer CD25-kappa+ immature B cells in tamoxifen-treated mice
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• fewer CD25+kappa- pre-B cells in tamoxifen-treated mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• tamoxifen-treated mice exhibit normal somatic hypermutation
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• tamoxifen-treated pro-B cells exhibit reduced survival compared with wild-type mice that cannot be rescued by expression of Bcl2 or Foxo1 or transformation with A-MuLV
• stimulated B cells from tamoxifen-treated mice exhibit reduced survival compared with control cells
• however, expression of Myb or BAFF rescues B cell survival and expression of Bcl2l1 partially rescues B survival
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• with cell cycle defects in tamoxifen-treated mice
• of B cells from tamoxifen-treated mice stimulated with LPS, CpG or anti-IgM
• tamoxifen-treated mice exhibit impaired germinal center formation and germinal center B cell proliferation compared with control mice
• however, B cell proliferation is rescued by transformation with A-MuLV
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• in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• of pre-B cells from tamoxifen-treated mice in vitro
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• in tamoxifen-treated mice, less severe 12 days after immunization
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• in tamoxifen-treated mice
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• reduced frequency of B220intCD43- pre-B cells in tamoxifen-treated mice
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• increased number of recirculating B220hiCD43- B cells in tamoxifen-treated mice
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• in immunized tamoxifen-treated mice
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• tamoxifen-treated mice exhibit impaired germinal center formation and germinal center B cell proliferation compared with control mice
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• by a factor of 5 in tamoxifen treated mice
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• by a factor of 3 in tamoxifen treated mice
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• tamoxifen-treated pro-B cells exhibit reduced survival compared with wild-type mice that cannot be rescued by expression of Bcl2 or Foxo1 or transformation with A-MuLV
• stimulated B cells from tamoxifen-treated mice exhibit reduced survival compared with control cells
• however, expression of Myb or BAFF rescues B cell survival and expression of Bcl2l1 partially rescues B survival
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• with cell cycle defects in tamoxifen-treated mice
• of B cells from tamoxifen-treated mice stimulated with LPS, CpG or anti-IgM
• tamoxifen-treated mice exhibit impaired germinal center formation and germinal center B cell proliferation compared with control mice
• however, B cell proliferation is rescued by transformation with A-MuLV
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• tamoxifen-treated pro-B cells exhibit reduced survival compared with wild-type mice that cannot be rescued by expression of Bcl2 or Foxo1 or transformation with A-MuLV
• stimulated B cells from tamoxifen-treated mice exhibit reduced survival compared with control cells
• however, expression of Myb or BAFF rescues B cell survival and expression of Bcl2l1 partially rescues B survival
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• with cell cycle defects in tamoxifen-treated mice
• of B cells from tamoxifen-treated mice stimulated with LPS, CpG or anti-IgM
• tamoxifen-treated mice exhibit impaired germinal center formation and germinal center B cell proliferation compared with control mice
• however, B cell proliferation is rescued by transformation with A-MuLV
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• in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• of pre-B cells from tamoxifen-treated mice in vitro
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• in tamoxifen-treated mice, less severe 12 days after immunization
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• in tamoxifen-treated mice
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• reduced frequency of B220intCD43- pre-B cells in tamoxifen-treated mice
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• increased number of recirculating B220hiCD43- B cells in tamoxifen-treated mice
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• in immunized tamoxifen-treated mice
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• tamoxifen-treated mice exhibit impaired germinal center formation and germinal center B cell proliferation compared with control mice
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• by a factor of 5 in tamoxifen treated mice
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• by a factor of 3 in tamoxifen treated mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following treatment with tamoxifen at E12.5, at E14.5 an increase in mitotic figures is seen in the neuroepithelium
• mitotic figures display an accumulation of prometaphases/metaphases
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• following treatment with tamoxifen at E12.5, at E14.5 an increase in mitotic figures is seen in the neuroepithelium
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• following treatment with tamoxifen at E12.5, at E14.5 an increase in mitotic figures is seen in the neuroepithelium
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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 03/25/2025 MGI 6.24 |
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