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Allele Symbol Allele Name Allele ID |
Klf4tm1Khk targeted mutation 1, Klaus H Kaestner MGI:2183917 |
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| Summary |
9 genotypes
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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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• decrease in both Ly6Chi and Ly6low blood and bone marrow monocytes as compared to controls
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• decrease in both Ly6Chi and Ly6low blood and bone marrow monocytes as compared to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hypertrophy is observed at 6 months
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• at 5 weeks, esophageal epithelia display hypertrophy with altered keratinocyte morphology with phenotype being stronger at 3 months
• at 6 months, a range of phenotypes from hyperplasia to moderate dysplasia with loss of surface keratinization
• basal cells show nuclear distortion and superficial cells have increased nuclear to cytoplasmic ratios, suggesting incomplete differentiation
• BrdU labeling shows increased number of proliferating cells in the basal layer, with a 1.9-fold increased measured at 3 months; compared to controls, increased apoptosis (2.7-fold) in esophageal epithelia is seen at 3 months
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• hypertrophy is observed at 6 months
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• seen at 6 months where skin lesions occur
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• hypertrophy is observed in squamous epithelium of skin on the ventral neck
• epithelia of skin on forestomach and back is normal at 6 months
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• seen in esophageal epithelia at 5 weeks
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• lesions (with crusting and moistness) are observed on parts of the face and skin on the ventral surface of the neck at 6 months
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• seen in esophageal epithelia at 5 weeks
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• hypertrophy is observed at 6 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in ex vivo assays, adhesion of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• in ex vivo assays, migration of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• after tamoxifen induction, the number and proliferation of hair follicles is increased compared to treated controls
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• in 6-8 week-old mutant mice after tamoxifen induction, the number and proliferation of hair follicles is increased compared to treated controls
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• suprabasal layer is multi-layered compared with single layer in controls
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• tamoxifen-treated mice show greater incidence and faster growth of DMBA/TPA-induced skin tumors compared with control animals (development by 12 weeks post treatment vs 15 weeks in controls; 80% of mice by 30 weeks vs 20% of controls); mutants demonstrate higher multiplicity (2 tumors/mouse vs 0.6/control) and greater size than controls
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• in tamoxifen-treated mutants, increased goblet cell proliferation is detected in the small intestine (inferred from increase in number and enlargement in size of Periodic acid-Schiff and Alcian Blue positive cells)
• neuroendocrine cells in the intestine are normal
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• mutants exhibit abnormal proliferation and differentiation of cell types in the small intestine including goblet, Paneth and stem cell/tuft cells; numbers are increased and loss of cell polarity and alterations in cell position are observed
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• increased numbers of Paneth cells are detected
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• Paneth cells are dislocated through crypt-villus axis
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• in tamoxifen-treated mutants, increased goblet cell proliferation is detected in the small intestine (inferred from increase in number and enlargement in size of Periodic acid-Schiff and Alcian Blue positive cells)
• neuroendocrine cells in the intestine are normal
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• in ex vivo assays, adhesion of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• in ex vivo assays, migration of ketatinocytes is increased in tamoxifen-treated cells relative to control cells
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• increased numbers of Paneth cells are detected
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• Paneth cells are dislocated through crypt-villus axis
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• tamoxifen-treated mice show greater incidence and faster growth of DMBA/TPA-induced skin tumors compared with control animals (development by 12 weeks post treatment vs 15 weeks in controls; 80% of mice by 30 weeks vs 20% of controls); mutants demonstrate higher multiplicity (2 tumors/mouse vs 0.6/control) and greater size than controls
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• after full-thickness wounds were introduced into the backs of tamoxifen-treated mutants and controls, wounds started to heal in control mice after 5 days with closure at 10 days whereas healing was significantly delayed in mutants; migration of cells toward the wound site occurs from both hair follicles and epidermal suprabasal layer
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• polypoid lesions of the mucosa are present at 1 year of age, but no inflammation, dysplasia, or malignancies are seen in the gastric epithelia at any time
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• by 6 months of age, exhibit severe distortion of gastric pit glands
• number of pit cells is increased about 2-fold
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• mature zymogenic cells are decreased by more than 50%
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• 50% decrease in the number of parietal cells
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• starting at 2 weeks of age, begin to show mucous cell hyperplasia
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• number of mucous neck cells per gland is increased 4-fold
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• exhibit increased proliferation and altered differentiation of the gastric epithelia
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• show progressive gastric hypertrophy beginning at 2 weeks of age
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• mutants display aberrant expression of acidic mucins and TFF2/SP-positive cells, indicative of premalignant conditions, but no inflammation, intestinal metaplasia, dysplasia, or cancer up to 1 year of age
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• by 6 months of age, exhibit severe distortion of gastric pit glands
• number of pit cells is increased about 2-fold
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• mature zymogenic cells are decreased by more than 50%
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• 50% decrease in the number of parietal cells
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• number of mucous neck cells per gland is increased 4-fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation
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• tamoxifen injected mice exhibit a marked (75%) but incomplete prevention of cerebral cavernous malformation lesion formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, the mutant corneal stroma is thinner with relatively fewer keratocytes relative to wild-type and single Klf5 conditional knockout corneas
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• mutant eyes fail to open as late as 35 weeks after birth, the latest stage examined
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• co-ablation of Klf4 and Klf5 in the ocular surface results in more severe eyelid and corneal abnormalities than those in either single conditional knockout
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• at 8 weeks of age, the mutant conjunctival epithelium is thinner than the wild-type or single Klf5 conditional knockout epithelium
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• at 8 weeks of age, conjunctiva goblet cells are missing
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• at 8 weeks of age, the mutant corneal epithelium is thinner than the wild-type and single Klf5 conditional knockout corneal epithelia, and remains fused to the eyelids
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, adult mutants display inflammation of the eyelids
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• at 8 weeks of age, enucleated mutant eyeballs appear marginally smaller and show a rough and speckled surface, unlike controls
• however, no major difference in eyelid fusion or the structure of the developing eye are noted at P1
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• at 8 weeks of age, about 20% of mutant eyes exhibit a hyperplastic iris causing the pupil to be smaller or absent in some eyes
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• at 8 weeks of age, about 20% of mutant eyes exhibit a hyperplastic iris
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• at 8 weeks of age, the conjunctiva lacks goblet cells, unlike in control mice
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• TEM shows that the basement layer beneath the epithelial cells is thinner in mutant corneas
• fewer and less-electron-dense hemidesmosomes connecting the basal epithelial cells to the basement membrane are observed in mutant corneas
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• at 8 weeks of age, the corneal endothelial cells are swollen and highly vacuolated
• however, the Descemet's membrane appears normal
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• epithelial bulli are occasionally observed in mutant corneas
• TEM indicates fewer corneal epithelium cell layers, fewer microvilli on the superficial cells, as well as swollen, spherical, and vacuolated basal cells, and a higher frequency of delamination than wild-type cells
• SEM of the corneal surface shows a mix of electron-dense and light cells, unlike the uniformly stained cells seen at the wild-type corneal surface
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• at 8 weeks of age, the corneal epithelium has 3 to 4 instead of the normal 5 to 8 cell layers
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• at 8 weeks of age, the corneal stroma is edematous, unlike in controls
• expression of the aquaporin-5 gene is downregulated, consistent with stromal edema
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• in the anterior stroma, the mean number of collagen fibrils per unit cross-sectional is reduced to ~70% of the wild-type number, resulting in higher interfibrillar space, consistent with stromal edema
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• at 8 weeks of age, the mean corneal stroma thickness is increased by 45%
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• at 8 weeks of age, the anterior cortical lens is vacuolated, unlike in control mice
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• at 8 weeks of age, the mutant lens shows vacuolated anterior cortical lens fiber cells beneath the epithelium, extending to the bow region, unlike the compactly packed fiber cells seen in the wild-type lens
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• at 8 weeks of age, the mean size of the mutant lens is decreased by about 12%
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• at 8 weeks of age, the mean size of the mutant eye is decreased by about 12%
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• a 2-fold increase in the number of BrdU-incorporating cells is noted in the corneal epithelium, suggesting that the reduced number of corneal epithelial cell layers is due to excessive cell sloughing rather than a reduced rate of cell proliferation
• expression of the keratin-12 gene is downregulated, consistent with corneal epithelial fragility
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• at 8 weeks of age, adult mutants display inflammation of the eyelids
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutant males show normal postnatal testis weights, with no significant differences in the ratio of testis weight to body weight or in Sertoli cell proliferation relative to control littermates
• notably, adult mutant males are fertile and yield litters of normal size and frequency relative to controls, despite reduced serum testosterone levels
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• at P18, mutant tubules exhibit a disorganized germinal epithelium with numerous vacuoles and no lumen
• however, no differences with regard to vacuolization of the cytoplasm or (dis-) organization of the germinal epithelium are noted in adult mutant tubules relative to controls, indicating that the phenotype observed at P18 is transient
• moreover, no significant differences are observed between the % of TUNEL-positive mutant tubules vs control tubules
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• whereas at P18 mutant tubules display a slightly, yet significantly increased diameter, at P20 mutant tubules exhibit a significantly reduced average diameter relative to control tubules
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• at P18, mutant Sertoli cells display a developmental delay in lumen formation with only 32% of mutant tubules exhibiting a lumen vs 75% of control tubules
• at P20, only 50% of mutant tubules display a lumen vs 87% of control tubules
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• gene expression profiling revealed differential expression of genes known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggesting impaired apical secretion of Sertoli cells
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• at P18, mutant tubules exhibit a disorganized germinal epithelium with numerous vacuoles and no lumen
• however, no differences with regard to vacuolization of the cytoplasm or (dis-) organization of the germinal epithelium are noted in adult mutant tubules relative to controls, indicating that the phenotype observed at P18 is transient
• moreover, no significant differences are observed between the % of TUNEL-positive mutant tubules vs control tubules
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• whereas at P18 mutant tubules display a slightly, yet significantly increased diameter, at P20 mutant tubules exhibit a significantly reduced average diameter relative to control tubules
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• at P18, mutant Sertoli cells display a developmental delay in lumen formation with only 32% of mutant tubules exhibiting a lumen vs 75% of control tubules
• at P20, only 50% of mutant tubules display a lumen vs 87% of control tubules
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• gene expression profiling revealed differential expression of genes known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggesting impaired apical secretion of Sertoli cells
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• at P56-P365, adult mutant males exhibit significantly reduced serum testosterone levels relative to control males
• in contrast, adult serum follicle stimulation hormone (FSH) and triiodothyronine (T3) levels remain relatively unaffected
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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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