Tetracycline response element driven Cre causes ectopic recombinase activity independent of transactivator element

Lewis, Kenneth T.; Oles, Lily R; MacDougald, Ormond A.

doi:10.1016/j.molmet.2022.101501

Cited by 5 publications

(4 citation statements)

References 48 publications

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“…However, given the ectopic activities of the Tyr and Dct promoters, the specificity of Cre recombination in such double transgenic mice might not be ideal. Furthermore, as it was reported recently, the TetO7::Cre driver line causes ectopic recombination even in the absence of a Dox‐inducible transactivator (Lewis et al, 2022). Therefore, in terms of the specificity of Cre recombination, the use of the Pmel P2A‐TetON3G‐TRE3G‐iCre mouse line is appropriate.…”

Section: Discussionmentioning

confidence: 67%

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

Nasrin

Ahmed

Han

et al. 2022

Pigment Cell Melanoma Res

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Melanocytes are melanin pigment-producing cells responsible for skin, hair, and eye pigmentation. Melanocytes also reside in the inner ear and heart, where they play important roles in maintaining auditory and cardiac functions (Levin et al., 2009;Tachibana, 1999).During development, precursors for pigment-producing melanocytes (melanoblasts) emerge in the neural crest and migrate throughout the embryo toward specific body locations where they finally reside.In mice, melanoblasts predominantly migrate into the developing hair follicles, where they form the hair follicle pigmentary unit together with surrounding keratinocytes and dermal cells to maintain the regenerative hair pigmentation cycle throughout life (Nishimura et al., 2002). Hair pigmentation is mediated by the melanogenic

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Section: Discussionmentioning

confidence: 67%

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

Nasrin

Ahmed

Han

et al. 2022

Pigment Cell Melanoma Res

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“…The tamoxifen system is generally preferred owing to its higher rate of induction [21,22] and specificity [23] among the inducible systems. Moreover, there may be trace amounts of tetracycline in mouse chow, leading to unintended 'leaky' expression of Cre recombinase.…”

Section: The Cre-loxp Systemmentioning

confidence: 99%

“…The use of a doxycyclineinducible system is relatively safer compared to using tamoxifen owing to the limited toxicity of doxycycline to humans. It is to be noted that both these systems are to some extent susceptible to inducer-independent 'leaky' Cre recombinase activity [23,31], with the tetracycline-inducible system being more susceptible to it. Therefore, the Cre expression in these mice should be thoroughly validated before studies on the downstream effects of the gene knockout.…”

Section: The Cre-loxp Systemmentioning

confidence: 99%

Benefits and Caveats in the Use of Retinal Pigment Epithelium-Specific Cre Mice

Kocherlakota,

Baes

2024

IJMS

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The retinal pigment epithelium (RPE) is an important monolayer of cells present in the outer retina, forming a major part of the blood–retina barrier (BRB). It performs many tasks essential for the maintenance of retinal integrity and function. With increasing knowledge of the retina, it is becoming clear that both common retinal disorders, like age-related macular degeneration, and rare genetic disorders originate in the RPE. This calls for a better understanding of the functions of various proteins within the RPE. In this regard, mice enabling an RPE-specific gene deletion are a powerful tool to study the role of a particular protein within the RPE cells in their native environment, simultaneously negating any potential influences of systemic changes. Moreover, since RPE cells interact closely with adjacent photoreceptors, these mice also provide an excellent avenue to study the importance of a particular gene function within the RPE to the retina as a whole. In this review, we outline and compare the features of various Cre mice created for this purpose, which allow for inducible or non-inducible RPE-specific knockout of a gene of interest. We summarize the various benefits and caveats involved in the use of such mouse lines, allowing researchers to make a well-informed decision on the choice of Cre mouse to use in relation to their research needs.

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“…Tetracycline-inducible Cre-recombinase constructs have been reported to have a degree of leakiness [24]. We tested this in our systems using two approaches.…”

Section: Testing Of Leakiness In Transgene Expressionmentioning

confidence: 99%

Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice

Sohail

Akkawi

Rechter

et al. 2023

IJMS

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Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 background) with a paired box 8 (PAX8) promoter. Body weights were not affected by the KO, but mean kidney weights were reduced in the KO mice (13 and 3%, in M and F, respectively, relative to wild-type (WT) mice). A microscopic analysis revealed 25 and 19% reductions in the proximal tubule (PT) and cortical collecting duct cell heights, respectively, in KOMs relative to WTMs. The reductions were 5 and 11% for KOFs. Western blotting of renal cortex homogenates showed decreased protein levels for the β and γ subunits of the epithelial sodium channel (ENaC) and the sodium-potassium-2-chloride cotransporter type 2 (NKCC2) in both sexes of KO mice; however, α-ENaC was upregulated in KOMs and downregulated in KOFs. Both sexes of KO mice cleared exogenously administered glucose faster than the WT mice and had lower semi-fasted, anesthetized blood glucose levels. However, KOMs (but not KOFs) demonstrated evidence of enhanced renal gluconeogenesis, including higher levels of renal glucose-6-phosphatase, the PT’s production of glucose, post-prandial blood glucose, and plasma insulin, whereas KOFs exhibited downregulation of renal high-capacity sodium glucose cotransporter (SGLT2) and upregulation of SGLT1; these changes appeared to be absent in the KOM. Overall, these findings suggest a sex-differential reliance on intact renal tubular InsR signaling which may be translationally important in type 2 diabetes, obesity, or insulin resistance when renal insulin signaling is reduced.

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Tetracycline response element driven Cre causes ectopic recombinase activity independent of transactivator element

Cited by 5 publications

References 48 publications

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

Benefits and Caveats in the Use of Retinal Pigment Epithelium-Specific Cre Mice

Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice

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