Book ChapterDOI
Cre/loxP recombination system and gene targeting.
Ralf Kühn,Raul M. Torres +1 more
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TLDR
The use of the Cre/loxP recombination system in conjunction with gene targeting has greatly expanded the versatility and avenues with which biologic questions can be addressed in the mouse.Abstract:
Embryonic stem (ES) cell technology has clearly established itself as a powerful technique for the examination of gene function in vivo. The vast majority of gene-targeting experiments to date have been designed simply to inactivate the function of the gene of interest by the targeted insertion of a selectable marker into the ES genome. Homologous recombinant ES cells are used without further modification for the generation of mice that bear a permanently modified allele in all cells from the onset of development. In contrast to this “conventional” gene-targeting strategy, in recent years, the use of the Cre/loxP recombination system in conjunction with gene targeting has greatly expanded the versatility and avenues with which biologic questions can be addressed in the mouse. In addition to the generation of subtle mutations, this system allows for a number of other genotypic options in ES cells or mice by strategically incorporating Cre recombinase recognition (loxP) sites into the genome and the subsequent expression of recombinase in vitro or in vivo. In particular, when Cre is expressed in mice harboring a loxP-containing target gene, the desired gene modification can be restricted to certain cell types or developmental stages of the mouse (conditional gene targeting) depending on the tissue specificity and timing of recombinase expression. There is no definitive rule to decide whether, for a particular experiment, conventional or conditional gene targeting is more appropriate since this depends on the specific biologic question and the peculiarities of the gene studied.read more
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Journal ArticleDOI
Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs.
Shiaoching Gong,Martin L. Doughty,Carroll R. Harbaugh,Alexander Cummins,Mary E. Hatten,Nathaniel Heintz,Charles R. Gerfen +6 more
TL;DR: These Cre driver lines add functional utility to the >500 BAC-EGFP (enhanced green fluorescent protein) transgenic mouse lines that are part of the Gene Expression Nervous System Atlas Project.
Journal ArticleDOI
Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement
I-hsin Su,Ashwin Basavaraj,Andrew N. Krutchinsky,Oliver Hobert,Axel Ullrich,Brian T. Chait,Alexander Tarakhovsky +6 more
TL;DR: Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development and rearrangements of the immunoglobulin heavy chain gene (Igh) are suggested.
Journal ArticleDOI
Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria
Carsten Merkwirth,Sascha Dargazanli,Takashi Tatsuta,Stefan Geimer,Beatrix Löwer,F. Thomas Wunderlich,Jiirgen-Christoph Von Kleist-Retzow,Ari Waisman,Benedikt Westermann,Thomas Langer +9 more
TL;DR: Conditional gene targeting of murine Phb2 is used to define cellular activities of prohibitins and assign an essential function for the formation of mitochondrial cristae to prohibitingins and suggest a coupling of cell proliferation to mitochondrial morphogenesis.
Journal ArticleDOI
NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism
Antonios O. Aliprantis,Yasuyoshi Ueki,Rosalyn Sulyanto,Arnold Park,Kirsten Sigrist,Sudarshana M. Sharma,Michael C. Ostrowski,Bjorn R. Olsen,Laurie H. Glimcher +8 more
TL;DR: It is demonstrated that NFATc1 is required for remodeling of the growing and adult skeleton and suggests that NF ATc1 may be an effective therapeutic target for osteoporosis associated with inflammatory states.
Journal ArticleDOI
Production of p53 gene knockout rats by homologous recombination in embryonic stem cells
TL;DR: The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provide a powerful new platform for the study of human disease.
References
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Journal ArticleDOI
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Peter Carmeliet,Valérie Ferreira,Georg Breier,Saskia Pollefeyt,Lena Kieckens,Marina Gertsenstein,Michaela Fahrig,Ann Vandenhoeck,Kendraprasad Harpal,Carmen Eberhardt,Cathérine Declercq,Judy Pawling,Lieve Moons,Desire Collen,Werner Risau,Andras Nagy,Andras Nagy +16 more
TL;DR: It is reported that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES)16,17, and even more impaired in homozygous D1-VEGF- deficient (VDGF-/-) T-ES embryos, resulting in death at mid-gestation.
Journal ArticleDOI
Inducible gene targeting in mice
TL;DR: A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented, which uses an interferon-responsive promoter to control the expression of Cre recombinase.
Journal ArticleDOI
The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory
TL;DR: The results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories.
Journal ArticleDOI
Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting
TL;DR: This work has shown that with the use of the bacteriophage-derived, site-specific recombinase Cre in a transgenic approach, the same mutation can be selectively introduced into a particular cellular compartment-in this case, T cells.