Efficient gene-specific expression of Cre recombinase in the mouse embryo by targeted insertion of a novel IRES-Cre cassette into endogenous loci

Michael, Simon K.; Brennan, Jane; Robertson, Elizabeth J.

doi:10.1016/s0925-4773(99)00052-0

Cited by 19 publications

(15 citation statements)

References 41 publications

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“…All PCR product incorporated in the final targeting vector was verified by bidirectional sequencing. Conditions for growth and electroporation of CCE embryonic stem cells, G418 selection, and preparation of chimeric mice were as described (30).…”

Section: Es Cellsmentioning

confidence: 99%

High blood pressure arising from a defect in vascular function

Michael

Surks

Wang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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126

146

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Hypertension, a major cardiovascular risk factor and cause of mortality worldwide, is thought to arise from primary renal abnormalities. However, the etiology of most cases of hypertension remains unexplained. Vascular tone, an important determinant of blood pressure, is regulated by nitric oxide, which causes vascular relaxation by increasing intracellular cGMP and activating cGMPdependent protein kinase I (PKGI). Here we show that mice with a selective mutation in the N-terminal protein interaction domain of PKGI␣ display inherited vascular smooth muscle cell abnormalities of contraction, abnormal relaxation of large and resistance blood vessels, and increased systemic blood pressure. Renal function studies and responses to changes in dietary sodium in the PKGI␣ mutant mice are normal. These data reveal that PKGI␣ is required for normal VSMC physiology and support the idea that high blood pressure can arise from a primary abnormality of vascular smooth muscle cell contractile regulation, suggesting a new approach to the diagnosis and therapy of hypertension and cardiovascular diseases.cyclic nucleotides ͉ hypertension ͉ nitric oxide ͉ vascular biology ͉ vascular smooth muscle E levated blood pressure is a major risk factor for cardiovascular diseases and is responsible for widespread morbidity and mortality (1). Blood pressure is regulated by a variety of complex neurohumoral and mechanical signals that together determine systemic vascular tone and resistance (2, 3). The prevailing model for elevated blood pressure states that renal abnormalities of sodium handling cause volume expansion, increased systemic vascular resistance, and hypertension, and a large number of physiologic and genetic studies support this model and the central role of the renal renin-angiotensinaldosterone system in blood pressure regulation (4-8). Changes in vascular morphology and tone can increase vascular resistance and blood pressure (5), but the hypothesis that primary abnormalities of vascular smooth muscle tone can cause hypertension has not been sufficiently tested (6).Vascular smooth muscle contraction is initiated by both calcium-dependent and -independent mechanisms. Increases in intracellular calcium from receptor-or ion channel-activated pathways (2) lead to activation of myosin light chain kinase, which phosphorylates myosin light chains, activating myosin ATPase and increasing vascular smooth muscle cell (VSMC) contraction and vascular tone. The central calcium-independent pathway regulating VSMC tension is mediated by the GTPase RhoA and Rho kinase, which promote VSMC differentiation, stress fiber formation, and contraction, also increasing vascular tone (2, 7). Conversely, VSMC relaxation is mediated by activation of myosin light chain phosphatase (MLCP), which dephosphorylates myosin light chains to cause relaxation. The relative proportion of phosphorylated and dephosphorylated myosin light chains thus determines the state of VSMC tone (reviewed in ref.2). Nitric oxide, the most important endogenous vasodilator, cause...

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Section: Es Cellsmentioning

confidence: 99%

High blood pressure arising from a defect in vascular function

Michael

Surks

Wang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

126

146

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“…Depending on the purpose of the fate mapping study, Cre/Flp are expressed in a gene-specific manner, allowing an individual cell type, distinct genetic lineage, or a particular spatial domain of a tissue to be indelibly marked. This level of spatial control is achieved by choosing an appropriate gene regulatory element to express Cre/Flp and making standard transgenic mice (e.g., Zinyk et al, 1998;Dymecki and Tomasiewicz, 1998) or knockin alleles by gene targeting (e.g., Michael et al, 1999;Kimmel et al, 2000). Several conditional Reporter alleles have been generated that contain a loxP-or frtflanked STOP cassette located upstream of various markers under the control of a promoter that is broadly expressed using transgenes or knockin alleles (e.g., lacZ, Soriano, 1999, or Rodriguez andDymecki, 2000; alkaline phosphatase, Lobe et al, 1999, or Awatramani et al, 2001; enhanced green fluorescent protein [eGFP], Novak et al, 2000, or Awatramani et al, 2003.…”

Section: Genetic Fate Mapping In Mouse: An Overviewmentioning

confidence: 99%

Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system

Joyner

Zervas

2006

Developmental Dynamics

172

167

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A fascinating aspect of developmental biology is how organs are assembled in three dimensions over time. Fundamental to understanding organogenesis is the ability to determine when and where specific cell types are generated, the lineage of each cell, and how cells move to reside in their final position. Numerous methods have been developed to mark and follow the fate of cells in various model organisms used by developmental biologists, but most are not readily applicable to mouse embryos in utero because they involve physical marking of cells through injection of tracers. The advent of sophisticated transgenic and gene targeting techniques, combined with the use of site-specific recombinases, has revolutionized fate mapping studies in mouse. Furthermore, using genetic fate mapping to mark cells has opened up the possibility of addressing fundamental questions that cannot be studied with traditional methods of fate mapping in other organisms. Specifically, genetic fate mapping allows both the relationship between embryonic gene expression and cell fate (genetic lineage) to be determined, as well as the link between gene expression domains and anatomy (genetic anatomy) to be established. In this review, we present the ever-evolving development of genetic fate mapping techniques in mouse, especially the recent advance of Genetic Inducible Fate Mapping. We then review recent studies in the nervous system (focusing on the anterior hindbrain) as well as in the limb and with adult stem cells to highlight fundamental developmental processes that can be discovered using genetic fate mapping approaches. We end with a look toward the future at a powerful new approach that combines genetic fate mapping with cellular phenotyping alleles to study cell morphology, physiology, and function using examples from the nervous system. Developmental Dynamics 235:2376 -2385, 2006.

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“…The Bmp7 cre/+ strain was generated by inserting an Internal Ribosomal Entry Site (IRES), Cre recombinase cDNA and FRTflanked PGK-hygromycin cassettes (Michael et al, 1999) into coding exon 1 of the Bmp7 gene. The targeting vector containing 3.5 kb 5′ and 4.5 kb 3′ homology arms (Godin et al, 1998) was transfected into CCE ES cells that were grown under drug selection as previously described (Michael et al, 1999).…”

Section: Mouse Strainsmentioning

confidence: 99%

“…The targeting vector containing 3.5 kb 5′ and 4.5 kb 3′ homology arms (Godin et al, 1998) was transfected into CCE ES cells that were grown under drug selection as previously described (Michael et al, 1999). Correctly targeted clones were identified by Southern hybridization and used to generate germ line chimeras.…”

Section: Mouse Strainsmentioning

confidence: 99%

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TGFβ superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population

et al. 2004

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The TGFβ superfamily plays diverse and essential roles in kidney development. Gdf11 and Bmp4 are essential for outgrowth and positioning of the ureteric bud, the inducer of metanephric mesenchyme. During nephrogenesis, Bmp7 is required for renewal of the mesenchyme progenitor population. Additionally, in vitro studies demonstrate inhibitory effects of BMPs and TGFβs on collecting duct branching and growth. Here,we explore the predicted models of TGFβ superfamily function by cell-specific inactivation of Smad4, a key mediator of TGFβsignaling. Using a HoxB7cre transgene expressed in ureteric bud and collecting duct, we find that development of the collecting duct is Smad4 independent. By contrast, removal of Smad4 in nephrogenic mesenchyme using the Bmp7cre/+ allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. Smad4-deficient metanephric mesenchyme does not display defects in inducibility in LiCl or spinal cord induction assays. However, in situ hybridization and lineage analysis of Smad4 null mesenchyme cells at E11.5 show that the nephrogenic mesenchyme does not aggregate tightly around the ureteric bud tips, but remains loosely associated, embedded within a population of cells expressing markers of both nephrogenic mesenchyme and peripheral stroma. We conclude that the failure of recruitment of nephrogenic mesenchyme leaves a primitive population of mesenchyme at the periphery of the kidney. This population is gradually depleted, and by E16.5 the periphery is composed of cells of stromal phenotype. This study uncovers a novel role for TGFβ superfamily signaling in the recruitment and/or organization of the nephrogenic mesenchyme at early time-points of kidney development. Additionally, we present conclusive genetic lineage mapping of the collecting duct and nephrogenic mesenchyme.

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Efficient gene-specific expression of Cre recombinase in the mouse embryo by targeted insertion of a novel IRES-Cre cassette into endogenous loci

Cited by 19 publications

References 41 publications

High blood pressure arising from a defect in vascular function

High blood pressure arising from a defect in vascular function

Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system

TGFβ superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population

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