Engineering a mouse balancer chromosome

Zheng, Binhai; Sage, Marijke; Cai, Wei-Wen; Thompson, Debrah M.; Tavsanli, Beril C.; Cheah, Yin-Chai; Bradley, Allan

doi:10.1038/11949

Cited by 134 publications

(98 citation statements)

References 26 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…acceptor and 147 bp of coding sequence fused to the vector backbone of the 5Ј hypoxanthine phosphoribosyltransferase (Hprt) vector (11,12) (Fig. 1 a and b).…”

Section: Resultsmentioning

confidence: 99%

“…Studies were licensed by the U.K. Home Office under the Animals (Scientific Procedures) Act 1986. The Prok2 targeting construct was generated as an insertional targeting vector incorporating the 5Ј Hprt chromosomal engineering cassette (11). A 2,362-bp 5Ј arm and 1,229-bp 3Ј arm were PCRamplified from a 129S7-derived BAC clone RPCI 21-497L12 by using Hi-Fidelity PCR mix (Invitrogen, Carlsbad, CA), and they were cloned into the 5Ј Hprt vector as a three-piece ligation.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei

Prosser

Bradley

Chesham

et al. 2007

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

Self Cite

130

138

View full text Add to dashboard Cite

The suprachiasmatic nucleus (SCN), the brain's principal circadian pacemaker, coordinates adaptive daily cycles of behavior and physiology, including the rhythm of sleep and wakefulness. The cellular mechanism sustaining SCN circadian timing is well characterized, but the neurochemical pathways by which SCN neurons coordinate circadian behaviors remain unknown. SCN transplant studies suggest a role for (unidentified) secreted factors, and one potential candidate is the SCN neuropeptide prokineticin 2 (Prok2). Prok2 and its cognate prokineticin receptor 2 (Prokr2/Gpcr73l1) are widely expressed in both the SCN and its neural targets, and Prok2 is light-regulated. Hence, they may contribute to cellular timing within the SCN, entrainment of the clock, and/or they may mediate circadian output. We show that a targeted null mutation of Prokr2 disrupts circadian coordination of the activity cycle and thermoregulation. Specifically, mice lacking Prokr2 lost precision in timing the onset of nocturnal locomotor activity; and under both a light/dark cycle and continuous darkness, there was a pronounced temporal redistribution of activity away from early to late circadian night. Moreover, the coherence of circadian behavior was significantly reduced, and nocturnal body temperature was depressed. Entrainment by light is not, however, dependent on Prokr2, and bioluminescence real-time imaging of organotypical SCN slices showed that the mutant SCN is fully competent as a circadian oscillator. We conclude that Prokr2 is not necessary for SCN cellular timekeeping or entrainment, but it is an essential link for coordination of circadian behavior and physiology by the SCN, especially in defining the onset and maintenance of circadian night.T he suprachiasmatic nucleus (SCN) of the hypothalamus constitutes an autonomous circadian pacemaker necessary for the maintenance of daily rhythms, including the cycle of sleep and wakefulness (1). The molecular basis of the cellular oscillator of the SCN is broadly characterized, but how the SCN signals circadian time to other sites in the brain and thence to peripheral tissues is unclear (2). Neuroanatomical projections from the SCN run predominantly to local hypothalamic and thalamic structures (3), including the dorsomedial nucleus (DMN), a principal site for the regulation of sleep and wakefulness and circadian arousal by behavioral cues (4, 5). How such ''hard-wired'' connections influence SCN targets remains open to question. Although electrical signaling by means of synaptic contacts is likely important (6), encapsulated SCN grafts unable to form synaptic contacts with host tissues are nevertheless able to establish circadian activity/rest cycles in previously arrhythmic, SCN-lesioned recipients (7). This finding indicates that paracrine factors from the SCN mediate circadian coordination within the brain. A small number of candidate factors have been explored, including TGF-␣ (8) and cardiotrophin-like cytokine (9). These factors are expressed by the SCN on a circadian basis, and local ...

show abstract

“…acceptor and 147 bp of coding sequence fused to the vector backbone of the 5Ј hypoxanthine phosphoribosyltransferase (Hprt) vector (11,12) (Fig. 1 a and b).…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei

Prosser

Bradley

Chesham

et al. 2007

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

Self Cite

130

138

View full text Add to dashboard Cite

show abstract

“…This finding was a major development for the experimental use of mice. Coat color mutations are still important as visible markers today, for example, as visible markers in general genetic analysis, as markers for the many different inbred lines developed since DBA, during the generation of mouse knockout mutations, and for the generation of mouse balancer chromosomes (Zheng et al, 1999;Hentges and Justice, 2004). Most importantly, however, coat color mutations have provided an opportunity to study the development and biology of an important, vertebrate-specific cell type, the melanocyte.…”

Section: Introductionmentioning

confidence: 99%

Mouse coat color mutations: From fancy mice to functional genomics

Steingrı́msson

Copeland

Jenkins

2006

Developmental Dynamics

View full text Add to dashboard Cite

Mouse coat color mutations have a long history in biomedical research. The viable and visible phenotype of most coat color mutations has made the pigment cell, the melanocyte, an ideal system for genetic, molecular, and cellular analysis. Molecular cloning and analysis of many of the different coat color mutations have revealed the roles of a diverse range of genes, and today we know more about the pathways and proteins that regulate the development and function of pigment cells than we know about most other cell types in mammalian organisms. Coat color mutations have also provided novel insights into stem cell biology and human diseases, including melanoma. In the future, it will be important to build on this history and knowledge by taking advantage of the extensive repertoire of recently developed genome-wide methodologies, available genomic information, and the powerful methods that have been developed for modifying the mouse genome to systematically dissect the development and function of this important cell type. The usefulness of coat color mutations has just begun to emerge. Developmental Dynamics 235: 2401-2411, 2006.

show abstract

“…These features ensure that chromosomes in trans to the balancer are transmitted intact and provide a convenient way to maintain stocks of lethal or sterile mutations. Although balancer chromosomes exist in other species (Zheng et al 1999;Wilson et al 2005;Edgley et al 2006), they have not been widely used outside of Drosophila because of the technical difficulty of generating such chromosomes.…”

mentioning

confidence: 99%

Traffic Lines: New Tools for Genetic Analysis inArabidopsis thaliana

Rossidivito

et al. 2015

Genetics

View full text Add to dashboard Cite

Genetic analysis requires the ability to identify the genotypes of individuals in a segregating population. This task is straightforward if each genotype has a distinctive phenotype, but is difficult if these genotypes are phenotypically similar or identical. We show that Arabidopsis seeds homozygous or heterozygous for a mutation of interest can be identified in a segregating family by placing the mutation in trans to a chromosome carrying a pair of seed-expressed green and red fluorescent transgenes (a "traffic line") that flank the mutation. Nonfluorescent seeds in the self-pollinated progeny of such a heterozygous plant are usually homozygous for the mutation, whereas seeds with intermediate green and red fluorescence are typically heterozygous for the mutation. This makes it possible to identify seedlings homozygous for mutations that lack an obvious seedling phenotype, and also facilitates the analysis of lethal or sterile mutations, which must be propagated in heterozygous condition. Traffic lines can also be used to identify progeny that have undergone recombination within a defined region of the genome, facilitating genetic mapping and the production of near-isogenic lines. We produced 488 transgenic lines containing single genome-mapped insertions of NAP:dsRED and NAP:eGFP in Columbia (330 lines) and Landsberg erecta (158 lines) and generated sets of traffic lines that span most regions of the Arabidopsis genome. We demonstrated the utility of these lines for identifying seeds of a specific genotype and for generating near-isogenic lines using mutations of WUSCHEL and SHOOTMERISTEMLESS. This new resource significantly decreases the effort and cost of genotyping segregating families and increases the efficiency of experiments that rely on the ability to detect recombination in a defined chromosomal segment.

show abstract

Engineering a mouse balancer chromosome

Cited by 134 publications

References 26 publications

Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei

Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei

Mouse coat color mutations: From fancy mice to functional genomics

Traffic Lines: New Tools for Genetic Analysis inArabidopsis thaliana

Contact Info

Product

Resources

About