In an animal model of cutaneous terminal differentiation, loss of the K14 promoter in DcKO embryos causes defects in epidermal granular and stratum corneum formation. Moreover, DcKO embryos do not acquire the barrier by E18.5. This finding suggests that a defect in K14 promoter may contribute to perinatal death. However, these findings are controversial.
Vegfr2 inhibits immune cell infiltration
To study whether a mutation in Vegfr2 inhibits immune cell infiltration, researchers in the DFF and DCKO mouse models assessed their tumors. They found that TPA increases tumorigenesis in the DMBA-induced chemical carcinogenesis model. TPA increased the number of CD45-positive inflammatory cells in DCKO mice after twice-weekly TPA treatments.
In a different study, DCKO mice displayed invasive and intramucosal cancers. The tumors regressed despite treatment. In DCKO mice, a lack of RBP/J expression in the skin was also a risk factor for ovarian cancer. In a similar manner, the DCKO mice showed reduced proliferative activity and were more susceptible to melanoma.
Distinct type of invasive cancer
The skin of DCKO mice displayed a distinct type of invasive cancer. The grafted RBP/J-mutated mice exhibited diminished nuclear C/EBPa immunolabeling. Furthermore, RBP/J cKO mice possessed decreased nuclear GTPa. Moreover, their embryos lacked DNA repair ability.
In another study, K18 and K6 were not induced in DcKO embryos. Neither K18 nor K6 were induced in DcKO skin, whereas K6 was induced in WT skin. The proteins in the skin of DCKO mice did not show signs of tumors. In contrast, the DCKO mRNA levels of K6 were two- to three times higher than those of WT mice.
Dltered epidermal morphology
In mice, DCKO mice display altered epidermal morphology. They display abnormal hyperproliferation and lack of K18. They also have impaired keratin-mediated cutaneous grafts. In these experiments, the grafts of RBP/J cKO embryos resemble cKO grafts. But the expression of these proteins was not altered in the skins of DCKO mice.
In a different study, DCKO mice developed non-polarised epidermis, displaying ectopic expression of K6. These abnormalities were also observed in other cell types. The grafted DCKO epidermis showed a decreased level of keratin filament bundles and keratohyalin granules. They were unable to develop properly at all stages of development.
In the RBP/J cKO mice, the RBP/J gene was not altered. The results were consistent with those in DCKO mice. The engrafted DcKO mice had impaired growth and reduced cellular activity. In addition, the DcKO mice developed a swollen tumor at six and nine months. The skins of these DCKO mice resemble those of the RBP/J cKOs.
Underlying gene dcko causes a tumor
In a DCKO mouse model, the underlying gene dcko causes a tumor to form in the epidermis. The gene is a key player in the development of cancer. When it is missing in the embryo, it can cause the disease to develop. There are several types of cellular tumours in DCKO mice, and the Dcko grafts of these tumours differ from the normal ones.
The phenotypes of DCKO mice include a distinct subset of AP-2a and AP-2g skin grafts. The epidermis of these DCKO embryos showed a weakened expression of nuclear C/EBPa. This, in turn, could indicate a genetic defect in RBP/J cKO mice. It is possible to reverse the effects of DcKO by genetically altering these genes.
The DcKO epidermis shows additional atypical perturbations. This suggests that the loss of AP-2 genes is the main cause of the keratinocytes’ dysfunction in the epidermis. It is unable to differentiate to the corresponding stage of atypical differentiation. The affected keratinocytes are not able to differentiate into spinous cells, which is the main reason for the deficiency in keratinocytes.
DcKO mice lack the AP-2 genes, which are important for the development of a healthy coat. In contrast, AP-2g DcKO mice did not develop a coat, and were phenotypically similar to wild-type mice. Although DcKO pups lacked whiskers, they were significantly smaller than single cKO mice. They also showed severe dehydration. If a person is unable to grow whiskers, they should consider a genetic disorder that affects the AP-2 gene.