A keratin K5Cre transgenic line appropriate for tissue‐specific or generalized cre‐mediated recombination

Ramı́rez, Ángel; Page, Angustias; Gandarillas, Alberto; Zanet, Jennifer; Pibre, Sophie; Vidal, Miguel; Tusell, Laura; Genescà, Anna; Whitaker, Duncan Andrew.; Melton, David W.; Jorcano, José L.

doi:10.1002/gene.20025

Cited by 176 publications

(223 citation statements)

References 19 publications

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“…Mice deficient in TNF (strain B6; 129S6-Tnf tm1Gkl /J), TNF-R1 and TNF-R2 (strain B6; 129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J), or TRIF (C57BL/6J-Ticam1 Lps2 /J [Hoebe et al, 2003]) and the ROSA26 reporter strain (B6.129S4-Gt(ROSA)26Sor tm1Sor /J) were obtained from The Jackson Laboratory. Mice expressing Cre under control of the K5 promoter (Ramirez et al, 2004) were obtained from J. Jorcano (Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain). Mice deficient in IL-1 and IL-1 (Yamada et al, 2000) were obtained from Y. Iwakura (Research Institute of Tuberculosis, Kiyose, Tokyo), and mice deficient in MyD88 were provided by S. Akira (Osaka University, Osaka, Japan).…”

Section: Materials and Methods Micementioning

confidence: 99%

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Kovalenko¹,

Kim²,

Kang³

et al. 2009

J Cell Biol

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Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor B activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8-deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8-deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency.

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Section: Materials and Methods Micementioning

confidence: 99%

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Kovalenko¹,

Kim²,

Kang³

et al. 2009

J Cell Biol

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“…Transgenic mice expressing the Cre recombinase under the control of the K5 promoter (K5-cre) were kindly provided by Dr. J. Jorcano [19], Rosa26LacZ reporter strain, carrying a loxP-stop-loxP-lacZ cassette, by P. Soriano [20], mycF/F strain, by I.M. de Alboran [21].…”

Section: Micementioning

confidence: 99%

The Proto-Oncogene Myc Is Essential for Mammary Stem Cell Function

et al. 2012

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The mammary epithelium comprises two major cell lineages: basal and luminal. Basal cells (BCs) isolated from the mammary epithelium and transplanted into the mouse mammary fat pad cleared from the endogenous epithelium regenerate the mammary gland, strongly suggesting that the basal epithelial compartment harbors a long-lived cell population with multipotent stem cell potential. The luminal cell layer is devoid of the regenerative potential, but it contains cells with clonogenic capacity, the luminal progenitors. Mammary BCs and luminal progenitors express high levels of the transcription factor Myc. Here, we show that deletion of Myc from mammary basal epithelial cells led to impaired stem cell self-renewal as evaluated by limiting dilution and serial transplantation assays. Luminal progenitor population was significantly diminished in mutant epithelium suggesting control by the BC layer. Colony formation assay performed with isolated BCs showed that clonogenic capacity was abolished by Myc deletion. Moreover, transplanted BCs depleted of Myc failed to produce epithelial outgrowths. Stimulation with ovarian hormones estrogen (E) and progesterone (P) partially rescued the repopulation capacity of Myc-depleted BCs; however, the Myc-deficient mammary epithelium developed in response to E/P treatment lacked stem and progenitor cells. This study provides the first evidence that in the mammary gland, Myc has an essential nonredundant function in the maintenance of the self-renewing multipotent stem cell population responsible for the regenerative capacity of the mammary epithelium and is required downstream from ovarian hormones, for the control of mammary stem and progenitor cell functions.

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“…To achieve keratinocyte-specific ablation, the C/ EBPb fl/fl mice were crossed with K5-Cre transgenic mice, in which Cre recombinase expression is directed to the epidermis and other stratified epithelia by the keratin 5 promoter (Ramirez et al, 2004). As shown in Figure 2a, C/EBPb protein was not detected in the epidermis of K5-Cre;C/EBPb fl/fl mice (faster mobility band in epidermis is non specific) but was present at normal levels in the other organs examined.…”

mentioning

confidence: 99%

Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

et al. 2005

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The CCAAT/enhancer binding protein b (C/EBPb) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBPb (C/EBPb À/À ) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBPb À/À mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBPb to specific phenotypes, mice with a conditional 'floxed' C/EBPb null allele were generated. Epidermal-specific deletion of C/EBPb was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBPb À/À mice, K5-Cre;C/ EBPb fl/fl mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBPd, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBPb in skin tumor development. Our findings demonstrate that C/EBPb exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBPb in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.

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A keratin K5Cre transgenic line appropriate for tissue‐specific or generalized cre‐mediated recombination

Cited by 176 publications

References 19 publications

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

The Proto-Oncogene Myc Is Essential for Mammary Stem Cell Function

Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

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