The origins of mouse genetics and the discovery of the T-locus

2022 ◽  
pp. 1-32
Author(s):  
Robert Erickson
Keyword(s):  
Mouse Genetics ◽  
T Locus

scholarly journals Phlogopite-pargasite coexistence in an oxygen reduced spinel-peridotite ambient

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Costanza Bonadiman ◽  
Valentina Brombin ◽  
Giovanni B. Andreozzi ◽  
Piera Benna ◽  
Massimo Coltorti ◽  
...  
Keyword(s):  
Oxygen Fugacity ◽  
Upper Mantle ◽  
Mantle Xenoliths ◽  
Spinel Peridotite ◽  
Simultaneous Formation ◽  
Empirical Potentials ◽  
Elastic Data ◽  
Mineralogical Study ◽  
Semi Empirical ◽  
T Locus

AbstractThe occurrence of phlogopite and amphibole in mantle ultramafic rocks is widely accepted as the modal effect of metasomatism in the upper mantle. However, their simultaneous formation during metasomatic events and the related sub-solidus equilibrium with the peridotite has not been extensively studied. In this work, we discuss the geochemical conditions at which the pargasite-phlogopite assemblage becomes stable, through the investigation of two mantle xenoliths from Mount Leura (Victoria State, Australia) that bear phlogopite and the phlogopite + amphibole (pargasite) pair disseminated in a harzburgite matrix. Combining a mineralogical study and thermodynamic modelling, we predict that the P–T locus of the equilibrium reaction pargasite + forsterite = Na-phlogopite + 2 diopside + spinel, over the range 1.3–3.0 GPa/540–1500 K, yields a negative Clapeyron slope of -0.003 GPa K–1 (on average). The intersection of the P–T locus of supposed equilibrium with the new mantle geotherm calculated in this work allowed us to state that the Mount Leura xenoliths achieved equilibrium at 2.3 GPa /1190 K, that represents a plausible depth of ~ 70 km. Metasomatic K-Na-OH rich fluids stabilize hydrous phases. This has been modelled by the following equilibrium equation: 2 (K,Na)-phlogopite + forsterite = 7/2 enstatite + spinel + fluid (components: Na2O,K2O,H2O). Using quantum-mechanics, semi-empirical potentials, lattice dynamics and observed thermo-elastic data, we concluded that K-Na-OH rich fluids are not effective metasomatic agents to convey alkali species across the upper mantle, as the fluids are highly reactive with the ultramafic system and favour the rapid formation of phlogopite and amphibole. In addition, oxygen fugacity estimates of the Mount Leura mantle xenoliths [Δ(FMQ) = –1.97 ± 0.35; –1.83 ± 0.36] indicate a more reducing mantle environment than what is expected from the occurrence of phlogopite and amphibole in spinel-bearing peridotites. This is accounted for by our model of full molecular dissociation of the fluid and incorporation of the O-H-K-Na species into (OH)-K-Na-bearing mineral phases (phlogopite and amphibole), that leads to a peridotite metasomatized ambient characterized by reduced oxygen fugacity.

scholarly journals Evolution of Mouse T-box Genes by Tandem Duplication and Cluster Dispersion

Genetics ◽  
1996 ◽  
Vol 144 (1) ◽  
pp. 249-254 ◽  
Author(s):  
Sergei I Agulnik ◽  
Nancy Garvey ◽  
Sarah Hancock ◽  
Ilya Ruvinsky ◽  
Deborah L Chapman ◽  
...  
Keyword(s):  
Tandem Duplication ◽  
Crossing Over ◽  
Dna Binding Domain ◽  
Gene Products ◽  
New Members ◽  
Ancestral Gene ◽  
T Box ◽  
Temporal And Spatial Patterns ◽  
Temporal And Spatial ◽  
T Locus

Abstract The T-box genes comprise an ancient family of putative transcription factors conserved across species as divergent as Mus musculus and Caenorhabditis elegans. All T-box gene products are characterized by a novel 174-186amino acid DNA binding domain called the T-box that was first discovered in the polypeptide products of the mouse T locus and the Drosophila melanogaster optomotor-blind gene. Earlier studies allowed the identification of five mouse T-box genes, T, Tbx1-3, and Tbr1, that all map to different chromosomal locations and are expressed in unique temporal and spatial patterns during embryogenesis. Here, we report the discovery of three new members of the mouse T-box gene family, named Tbx4, Tbx5, and Tbx6. Two of these newly discovered genes, Tbx4 and Tbx5, were found to be tightly linked to previously identified T-box genes. Combined results from phylogenetic, linkage, and physical mapping studies provide a picture for the evolution of a T-box subfamily by unequal crossing over to form a two-gene cluster that was duplicated and dispersed to two chromosomal locations. This analysis suggests that Tbx4 and Tbx5 are cognate genes that diverged apart from a common ancestral gene during early vertebrate evolution.

scholarly journals Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Carmelo Bellardita ◽  
Vittorio Caggiano ◽  
Roberto Leiras ◽  
Vanessa Caldeira ◽  
Andrea Fuchs ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Neural Activity ◽  
Sensory Input ◽  
Mouse Genetics ◽  
Spinal Interneurons ◽  
Neuronal Mechanisms ◽  
Cord Injury ◽  
Motor Neuron Excitability ◽  
Spinal Network ◽  
Opening Up

Spasms after spinal cord injury (SCI) are debilitating involuntary muscle contractions that have been associated with increased motor neuron excitability and decreased inhibition. However, whether spasms involve activation of premotor spinal excitatory neuronal circuits is unknown. Here we use mouse genetics, electrophysiology, imaging and optogenetics to directly target major classes of spinal interneurons as well as motor neurons during spasms in a mouse model of chronic SCI. We find that assemblies of excitatory spinal interneurons are recruited by sensory input into functional circuits to generate persistent neural activity, which interacts with both the graded expression of plateau potentials in motor neurons to generate spasms, and inhibitory interneurons to curtail them. Our study reveals hitherto unrecognized neuronal mechanisms for the generation of persistent neural activity under pathophysiological conditions, opening up new targets for treatment of muscle spasms after SCI.

scholarly journals THE ROLE OF INTERLEUKIN 1β GENE POLYMORPHISM IN DEVELOPMENT OF PREDOMINANTY SENSORY CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

2019 ◽  
Vol 21 (1) ◽  
pp. 141-148
Author(s):  
T. E. Popova ◽  
N. A. Shnayder ◽  
M. M. Petrova ◽  
A. A. Tappakhov
Keyword(s):  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Study Groups ◽  
Krasnoyarsk Region ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Disease ◽  
T Locus ◽  
Il1b Gene

The aim of the present study was a search for associations between the polymorphic allelic variants 3954 C>T (rs1143644) and -511C>T (rs16944) of IL1B gene in the patients with sensory predominant chronic inflammatory demyelinating polyneuropathies (SP-CIDP) from Krasnoyarsk Region and the Sakha (Yakutia) Republic. A total of 95 people were examined, having been divided into 2 groups according to their residence. The first group consisted of 42 patients living in the Sakha (Yakutia) Republic. The second group included 53 patients living in the Krasnoyarsk Region. It was revealed that the carriers of homozygous CC genotype in the 3954C>T locus were more often detected in patients from the Sakha (Yakutia) Republic, and the carriage of TT genotype is found exclusively in the patients from Krasnoyarsk Region. When comparing the different genotype frequencies in the -511CT locus, we did not reveal any statistically significant differences between the two groups of patients. Presence of the CC genotype of the 3954C>T locus was associated with a significantly increased risk of disease in the patients from Sakha (Yakutia) Republic, while carrying CT and TT genotypes at the locus 3954C>T and the TT genotype at the locus -511C>T, is associated with increased risk disorder among patients of the Krasnoyarsk Region. The frequency of carriage of various genotypes in the 3954C>T and -511C>T loci of the IL1B gene was prevalent among the patients from the Sakha (Yakutia) Republic, the association of genotypes of CC/CT prevailed in patients from the Krasnoyarsk Region (p = 0.005), as well as prevalence of CC/CC and CC/CT (p = 0.023). However, there was no statistically significant difference in occurrence of individual genotypes between the two study groups. When analyzing the carrier frequency of high-producing alleles of 3954C and -511C in patients with SP-CIDP, it was shown that they were significantly more common among patients from the Sakha (Yakutia) Republic and patients from the Krasnoyarsk Region than the low-producing 3954T and -511T alleles. Moreover, the 3954C allele was more often found in the Yakut group (p = 0.001), and in the -511C allele for the Krasnoyarsk group of patients (p = 0.05). The presence of 3954C and -511C alleles increases the risk of SP-CIDP development in patients from the Sakha (Yakutia) Republic, as well as carriage of 3954T allele in patients from the Krasnoyarsk Region.

scholarly journals Plexin-B1 mutation drives prostate cancer metastasis

2020 ◽  
Author(s):  
Boris Shorning ◽  
Neil Trent ◽  
David Griffiths ◽  
Thomas Worzfeld ◽  
Stefan Offermanns ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Metastasis ◽  
Locally Advanced ◽  
Tumour Cells ◽  
Mouse Genetics ◽  
The Body ◽  
Cancer Type ◽  
Wild Type ◽  
Tumour Spread ◽  
Mouse Prostate

AbstractProstate cancer mortality is associated with the metastatic spread of tumour cells. A better understanding of the mechanisms which allow a locally advanced tumour to disseminate around the body will identify new therapeutic targets to block this process. One of set of genes implicated in metastasis are plexins, which can promote or suppress tumour progression depending on cancer type and cellular context. We have taken a mouse genetics approach to gain insight into the role of Plexin-B1 in prostate cancer progression in vivo.We show here that genetic deletion of Plexin-B1 in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mouse prostate cancer models significantly decreased metastasis. High levels of prostate epithelial cell-specific expression of wild-type Plexin-B1 in knock-in mice with a PbCre+Ptenfl/flKrasG12V background also significantly decreased metastasis. In contrast, expression of a Plexin-B1 mutant (P1597L; identified from metastatic deposits in prostate cancer patients) in prostate epithelial cells in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mice significantly increased metastasis, in particular metastasis to distant sites. In line with these findings, both deletion and overexpression of wild-type Plexin-B1 reduced invasion of tumour cells into the prostate stroma, while overexpression of mutant Plexin-B1 significantly increased invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Invasion and metastasis also correlated with phosphorylation of myosin light chain, suggesting that Plexin-B1 signals via the Rho/ROCK pathway to promote metastasis.Our results demonstrate that mutant Plexin-B1 promotes metastasis in prostate cancer and represents a new therapeutic target to suppress tumour spread.

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