Table 1.
Tissue Studied | Targeted Gene | Mouse Model Used | Observed Phenotypes | Biological Process Affected | References |
---|---|---|---|---|---|
Intestine | Ring1a/b |
Ring1a−/−;Ring1bfl/fl; LGR5-eGFP-IRES-CreERT2 |
lower body weight, thinner intestine, defect in crypt architecture | reduced self-renewal and proliferation of intestinal stem cells, expression of non-lineage transcription factors | Chiacchiera et al., 2016 [22] |
Eed | Eedfl/fl; AhCre | alteration in crypt-villus architecture, expansion of goblet cell and enteroendocrine cells | reduced proliferation of transit amplifying cells, lowered secretory lineage commitment | Chiacchiera et al., 2016 [157] | |
Eed | Eedfl/fl; AhCre | lower body weight, extensive crypt and microcystic degeneration, necrosis, hypertrophy, and hyperplasia of crypts | reduced proliferation of intestinal crypt cells | Koppens et al., 2016 [20] | |
Bone marrow stromal cells | Bmi1 | Bmi1fl/fl; Prx1-Cre | accumulation of bone marrow adipocytes, reduction in bone marrow cellularity | increased senescence, depletion of HSCs and progenitor cells, increased adipogenic differentiation | Hu et al., 2019 [158] |
Hematopoietic cells | Bmi1 |
Vav-Cre;Rosa26StopFLBmi1 (over-expression of Bmi1) |
reduction in age-related anemia | attenuated age-related HSC function, maintenance of HSC signature gene expression | Nitta et al., 2020 [159] |
Eed | Eedfl/fl; CreERT2 | thymic and splenic atrophy, pale bone marrow, hematopoietic dysplasia | reduction in all hematopoietic cellular lineages, abnormal cell cycle, upregulation of adhesion molecule genes | Ikeda et al., 2016 [160] |
|
Phf19 | Phf19−/− | high penetrance of splenomegaly | upregulation of retinoic acid pathway, downregulation of Myc network and genes related to biosynthesis and energy production | Vizán et al., 2020 [161] |
|
Interfollicular epidermis | Eed and Ring1a/b |
Eedfl/fl; K14-CreERT2 and Ring1a−/−;Ring1bfl/fl; K14-CreERT2 |
epidermal pigmentation | upregulation of UV-responsive genes in EpSCs, induction of COL2A1 expression which promotes epidermal pigmentation | Li et al., 2021 [162] |
Interfollicular epidermis and hair follicle | Jarid2 | Jarid2fl/fl; K14CreYFP::Rosa26 | defective epidermal thickness and delayed hair cycle | reduced proliferation of basal cells of the epidermis and hair germ cells of the hair follicle, enhanced differentiation of basal cells | Mejetta et al., 2011 [163] |
Hair follicle | Ring1a/b |
Ring1a−/−;Ring1bfl/fl; LGR5-eGFP-IRES-CreERT2 |
arrested hair follicle growth | defective Lgr5+ HFSC differentiation due to upregulation of non-lineage genes | Pivetti et al., 2019 [164] |
Incisors | Ring1a/b |
Ring1a−/−;Ring1bfl/fl; Rosa26::CreERT2 |
Defective enamel and dentin formation | Reduced proliferation of mesenchymal transit amplifying cells | Lapthanasupkul et al., 2012 [165], An et al., 2018 [166] |
Bmi1 | Bmi1GFP/GFP (Bmi1-null mice) | defective enamel production | fewer stem cells due to upregulation of Ink4a/Arf, upregulation of Hox genes leading to premature differentiation and loss of stem cell population | Biehs et al., 2013 [167] |