scholarly journals Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1911-1921 ◽  
Author(s):  
E. van Den Akker ◽  
C. Fromental-Ramain ◽  
W. de Graaff ◽  
H. Le Mouellic ◽  
P. Brulet ◽  
...  
Keyword(s):  
Hox Genes ◽  
Lumbar Vertebrae ◽  
The Other ◽  
Axial Position ◽  
Loss Of Function ◽  
Axial Region ◽  
Unique Role ◽  
Paralogous Group ◽  
Upper Thoracic ◽  
Redundant Functions

We present a detailed study of the genetic basis of mesodermal axial patterning by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 loss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice. Our analysis of single mutants reveals common features for the Hoxc8 and Hoxd8 genes in patterning lower thoracic and lumbar vertebrae. In the Hoxb8 mutant, more anterior axial regions are affected. The three paralogous Hox genes are expressed up to similar rostral boundaries in the mesoderm, but at levels that strongly vary with the axial position. We find that the axial region affected in each of the single mutants mostly corresponds to the area with the highest level of gene expression. However, analysis of double and triple mutants reveals that lower expression of the other two paralogous genes also plays a patterning role when the mainly expressed gene is defective. We therefore conclude that paralogous group 8 Hox genes are involved in patterning quite an extensive anteroposterior (AP) axial region. Phenotypes of double and triple mutants reveal that Hoxb8, Hoxc8 and Hoxd8 have redundant functions at upper thoracic and sacral levels, including positioning of the hindlimbs. Interestingly, loss of functional Hoxb8 alleles partially rescues the phenotype of Hoxc8- and Hoxc8/Hoxd8-null mutants at lower thoracic and lumbar levels. This suggests that Hoxb8 affects patterning at these axial positions differently from the other paralogous gene products. We conclude that paralogous Hox genes can have a unique role in patterning specific axial regions in addition to their redundant function at other AP levels.

scholarly journals act Operon Control of Developmental Gene Expression in Myxococcus xanthus

2002 ◽  
Vol 184 (4) ◽  
pp. 1172-1179 ◽  
Author(s):  
Thomas M. A. Gronewold ◽  
Dale Kaiser
Keyword(s):  
Fruiting Body ◽  
Myxococcus Xanthus ◽  
The Other ◽  
Loss Of Function ◽  
Wild Type ◽  
Developmental Gene ◽  
Developmental Gene Expression ◽  
Mutant Strains ◽  
Genes Encoding ◽  
Signal Production

ABSTRACT Cell-bound C-signal guides the building of a fruiting body and triggers the differentiation of myxospores. Earlier work has shown that transcription of the csgA gene, which encodes the C-signal, is directed by four genes of the act operon. To see how expression of the genes encoding components of the aggregation and sporulation processes depends on C-signaling, mutants with loss-of-function mutations in each of the act genes were investigated. These mutations were found to have no effect on genes that are normally expressed up to 3 h into development and are C-signal independent. Neither the time of first expression nor the rate of expression increase was changed in actA, actB, actC, or actD mutant strains. Also, there was no effect on A-signal production, which normally starts before 3 h. By contrast, the null act mutants have striking defects in C-signal production. These mutations changed the expression of four gene reporters that are related to aggregation and sporulation and are expressed at 6 h or later in development. The actA and actB null mutations substantially decreased the expression of all these reporters. The other act null mutations caused either premature expression to wild-type levels (actC) or delayed expression (actD), which ultimately rose to wild-type levels. The pattern of effects on these reporters shows how the C-signal differentially regulates the steps that together build a fruiting body and differentiate spores within it.

Genetic analysis of Pycr1 and Pycr2 in mice

Genetics ◽  
2021 ◽  
Author(s):  
Morgane G Stum ◽  
Abigail L D Tadenev ◽  
Kevin L Seburn ◽  
Kathy E Miers ◽  
Pak P Poon ◽  
...  
Keyword(s):  
Neuromuscular Disorders ◽  
Subcutaneous Fat ◽  
Mutant Mice ◽  
Loss Of Function ◽  
Proline Biosynthesis ◽  
Cell Counts ◽  
Chemically Induced ◽  
White Blood Cell Counts ◽  
Redundant Functions ◽  
Altered Lipid

Abstract The final step in proline biosynthesis is catalyzed by three pyrroline-5-carboxylate reductases, PYCR1, PYCR2, and PYCR3, which convert pyrroline-5-carboxylate (P5C) to proline. Mutations in human PYCR1 and ALDH18A1 (P5C Synthetase) cause Cutis Laxa (CL), whereas mutations in PYCR2 cause hypomyelinating leukodystrophy 10 (HLD10). Here, we investigated the genetics of Pycr1 and Pycr2 in mice. A null allele of Pycr1 did not show integument or CL-related phenotypes. We also studied a novel chemically-induced mutation in Pycr2. Mice with recessive loss-of-function mutations in Pycr2 showed phenotypes consistent with neurological and neuromuscular disorders, including weight loss, kyphosis, and hind-limb clasping. The peripheral nervous system was largely unaffected, with only mild axonal atrophy in peripheral nerves. A severe loss of subcutaneous fat in Pycr2 mutant mice is reminiscent of a CL-like phenotype, but primary features such as elastin abnormalities were not observed. Aged Pycr2 mutant mice had reduced white blood cell counts and altered lipid metabolism, suggesting a generalized metabolic disorder. PYCR1 and -2 have similar enzymatic and cellular activities, and consistent with previous studies, both were localized in the mitochondria in fibroblasts. Both PYCR1 and -2 were able to complement the loss of Pro3, the yeast enzyme that converts P5C to proline, confirming their activity as P5C reductases. In mice, Pycr1; Pycr2 double mutants were sub-viable and unhealthy compared to either single mutant, indicating the genes are largely functionally redundant. Proline levels were not reduced, and precursors were not increased in serum from Pycr2 mutant mice or in lysates from skin fibroblast cultures, but placing Pycr2 mutant mice on a proline-free diet worsened the phenotype. Thus, Pycr1 and -2 have redundant functions in proline biosynthesis, and their loss makes proline a semi-essential amino acid. These findings have implications for understanding the genetics of CL and HLD10, and for modeling these disorders in mice.

scholarly journals The conception of substitution of the equals sign plays a unique role in students' algebra performance

2019 ◽  
Vol 5 (1) ◽  
pp. 24-37 ◽  
Author(s):  
Emine Simsek ◽  
Iro Xenidou-Dervou ◽  
Ilyas Karadeniz ◽  
Ian Jones
Keyword(s):  
Secondary School ◽  
Secondary School Students ◽  
The Other ◽  
School Students ◽  
Unique Role ◽  
School Year ◽  
Equals Sign ◽  
Definition Of ◽  
Unique Predictor ◽  
Algebra Learning

Students’ conceptions of the equals sign are related to algebraic success. Research has identified two common conceptions held by children: operational and relational. The latter has been widely operationalised in terms of the sameness of the values on each side of the equals sign, but it has been recently argued that the substitution component of relational equivalence should also be operationalised (Jones, Inglis, Gilmore, & Dowens, 2012, https://doi.org/10.1016/j.jecp.2012.05.003). In this study, we investigated whether students’ endorsement of the substitution definition of the equals sign is a unique predictor of their algebra performance independent of the other two definitions (operational and sameness). Secondary school students were asked to rate the ‘cleverness’ of operational, sameness, and substitution definitions of the equals sign and completed an algebra test. Our findings demonstrate that endorsement of substitution plays a unique role in explaining secondary school students’ algebra performance above and beyond school year and the other definitions. These findings contribute new insights into how students’ algebra learning relates to their conceptions of the equals sign.

scholarly journals Characterization of an Unstable Allele of the Arabidopsis HY4 Locus

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1575-1585
Author(s):  
Edward P Bruggemann ◽  
Bernard Doan ◽  
Korie Handwerger ◽  
Gisela Storz
Keyword(s):  
Fast Neutron ◽  
Blue Light ◽  
Large Deletion ◽  
The Other ◽  
Epigenetic Mechanisms ◽  
Loss Of Function ◽  
Wild Type ◽  
Unusual Behavior ◽  
Recessive Lethal

Abstract The Arabidopsis HY4 gene encodes the nonessential blue light photoreceptor CRY1. Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after germination under blue light. We previously analyzed 20 independent hy4 alleles produced by fast neutron mutagenesis. These alleles were grouped into two classes based on their genetic behavior and corresponding deletion size: (1) null hy4 alleles that were semidominant over wild type and contained small or moderate-sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and contained large HY4 deletions. Here we describe one additional fast neutron hy4 mutant, B144, that did not fall into either of these two classes. Mutant B144 was isolated as a heterozygote with an intermediate hy4 phenotype. One allele from this mutant, hy4-B144Δ, contains a large deletion at HY4 and is recessive lethal. The other allele from this mutant, HY4-B144*, appears to be intact and functional but is unstable and spontaneously converts to a nonfunctional hy4 allele. In addition, HY4-B144* is lethal in homozygotes and suppresses local recombination. We discuss genetic and epigenetic mechanisms that may account for the unusual behavior of the HY4-B144* allele.

Loss of Function of the Homeobox Gene Hoxa-9 Perturbs Early T-Cell Development and Induces Apoptosis in Primitive Thymocytes

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 383-393 ◽  
Author(s):  
David J. Izon ◽  
Sofia Rozenfeld ◽  
Stephen T. Fong ◽  
László Kömüves ◽  
Corey Largman ◽  
...  
Keyword(s):  
T Cell ◽  
Hox Genes ◽  
Apoptotic Cell ◽  
T Cell Development ◽  
Interleukin 2 ◽  
Homeobox Gene ◽  
Cell Receptor ◽  
Cell Development ◽  
Loss Of Function ◽  
Double Positive

Abstract Hox homeobox genes play a crucial role in specifying the embryonic body pattern. However, a role for Hox genes in T-cell development has not been explored. The Hoxa-9 gene is expressed in normal adult and fetal thymuses. Fetal thymuses of mice homozygous for an interruption of the Hoxa-9 gene are one eighth normal size and have a 25-fold decrease in the number of primitive thymocytes expressing the interleukin-2 receptor (IL-2R, CD25). Progression to the double positive (CD4+CD8+) stage is dramatically retarded in fetal thymic organ cultures. This aberrant development is associated with decreased amounts of intracellular CD3 and T-cell receptor β (TCRβ) and reduced surface expression of IL-7R and E-cadherin. Mutant thymocytes show a significant increase in apoptotic cell death and premature downregulation of bcl-2 expression. A similar phenotype is seen in primitive thymocytes from adult Hoxa-9−/− mice and from mice transplanted with Hoxa-9−/−marrow. Hoxa-9 appears to play a previously unsuspected role in T-cell ontogeny by modulating cell survival of early thymocytes and by regulating their subsequent differentiation.

Grouting Technique Applications during Housing Construction

2015 ◽  
Vol 724 ◽  
pp. 53-56
Author(s):  
Qin Zhang ◽  
Lin Li ◽  
You Mo
Keyword(s):  
The Other ◽  
Housing Construction ◽  
Specific Pressure ◽  
Unique Role ◽  
Construction Period ◽  
Small Opening ◽  
Loose Soil ◽  
Other Substances ◽  
Inherent Nature

The housing construction grouting technique is to select a specific pressure feed approach to pour the slurry in gel into the loose soil or the rock cracks with water. The slurry, through condensation and the particles consolidation in this category, will be filled into the rock cracks in the section so as to improve the inherent nature of the soil and the mechanical properties of the other substances. During the construction period, the slurry can be fed into the injected holes within this segment through the unique role of the pressure. The small opening surrounding the grouting holes, the preset requirements will be met. Therefore, it is necessary to clarify the specific applications of grouting techniques.

scholarly journals Correction to: DNMT3A reads and connects histone H3K36me2 to DNA methylation

2019 ◽  
Vol 11 (3) ◽  
pp. 230-230
Author(s):  
Wenqi Xu ◽  
Jiahui Li ◽  
Bowen Rong ◽  
Bin Zhao ◽  
Mei Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Mark ◽  
The Other ◽  
Therapeutic Implication ◽  
Loss Of Function ◽  
Function Model ◽  
Gain Of Function ◽  
Intergenic Dna ◽  
Preferential Recognition ◽  
Function Models

The author would like to add the below information in this correction. A similar study from Chao Lu group was published online on 5 September 2019 in Nature, entitled “The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape” (Weinberg et al., 2019). Although both the studies reported the preferential recognition of H3K36me2 by DNMT3A PWWP, ours in addition uncovered a stimulation function by such interaction on the activity of DNMT3A. On the disease connections, we used a NSD2 gain-of-function model which led to the discovery of potential therapeutic implication of DNA inhibitors in the related cancers, while the other study only used NSD1 and DNMT3A loss-of-function models.

scholarly journals Dorsoventral decoupling of Hox gene expression underpins the diversification of molluscs

2019 ◽  
Vol 117 (1) ◽  
pp. 503-512 ◽  
Author(s):  
Pin Huan ◽  
Qian Wang ◽  
Sujian Tan ◽  
Baozhong Liu
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Dorsal Side ◽  
The Other ◽  
Strongly Correlated ◽  
Expression Data ◽  
Shell Formation ◽  
Hox Gene ◽  
Evolutionary Diversification

In contrast to the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns with differences reported among lineages. Here, we investigate 2 phylogenetically distant molluscs, a gastropod and a polyplacophoran, and show that the Hox expression in both species can be divided into 2 categories. The Hox expression in the ventral ectoderm generally shows a canonical staggered pattern comparable to the patterns of other bilaterians and likely contributes to ventral patterning, such as neurogenesis. The other category of Hox expression on the dorsal side is strongly correlated with shell formation and exhibits lineage-specific characteristics in each class of mollusc. This generalized model of decoupled dorsoventral Hox expression is compatible with known Hox expression data from other molluscan lineages and may represent a key characteristic of molluscan Hox expression. These results support the concept of widespread staggered Hox expression in Mollusca and reveal aspects that may be related to the evolutionary diversification of molluscs. We propose that dorsoventral decoupling of Hox expression allowed lineage-specific dorsal and ventral patterning, which may have facilitated the evolution of diverse body plans in different molluscan lineages.

Abductor Pollicis Longus: A Case of Mistaken Identity

1992 ◽  
Vol 17 (4) ◽  
pp. 476-478 ◽  
Author(s):  
B. G. ELLIOTT
Keyword(s):  
The Other ◽  
Loss Of Function ◽  
Mistaken Identity ◽  
Abductor Pollicis Longus ◽  
Radial Deviation

Abductor pollicis longus, long regarded as a motor for the thumb, is anatomically and functionally a radial deviator of the wrist and should be so named. The abductor carpi is proposed. If the other radial deviators of the wrist are acting this tendon can be selectively utilized as a transfer without loss of function. Reflex spasm of this muscle probably plays an important role in the radial deviation deformity seen in the rheumatoid hand.

scholarly journals Multiple steroid-binding orientations: alteration of regiospecificity of dehydroepiandrosterone 2- and 7-hydroxylase activities of cytochrome P-450 2a-5 by mutation of residue 209

1995 ◽  
Vol 306 (1) ◽  
pp. 29-33 ◽  
Author(s):  
M Iwasaki ◽  
D G Davis ◽  
T A Darden ◽  
L G Pedersen ◽  
M Negishi
Keyword(s):  
Dynamic Equilibrium ◽  
The Other ◽  
Axial Position ◽  
Hydroxylase Activity ◽  
Steroid Molecule ◽  
Multiple Binding ◽  
Critical Residues ◽  
Steroid Binding ◽  
Binding Orientations ◽  
Cytochrome P 450

The mutation of Ala-117 to Val conferred dehydroepiandrosterone (DHEA) hydroxylase activity on cytochrome P-450 2a-4, with the production of both 2 alpha- and 7 alpha-hydroxyDHEA at similar rates. P-450 2a-5 which has Val at position 117, acquired high DHEA hydroxylase activity by mutation of Phe-209. Mutant F209L of P-450 2a-5 exhibited strong regiospecificity at the 2-position of the DHEA molecule with the production of 2 alpha-hydroxy DHEA as the major metabolite. On the other hand, mutant F209V of P-450 2a-5 showed the 7-position to be the major hydroxylation site, 7 beta-hydroxyDHEA and 7 alpha-OHDHEA being produced. Therefore the regiospecificity of DHEA hydroxylase activity of P-450 2a-5 is altered between the 2- and 7-position depending on the amino acid at position 209. Modelling of the DHEA molecule in the pocket of bacterial P-450cam showed that the steroid can be accommodated in at least two orientations for which the 2- or 7- position is near the sixth axial position of the haem. Moreover, these two orientations, which are of similar energy, can be interconverted by a 180 degrees rotation of the steroid molecule around its long axis. These results support the hypothesis that the steroid molecule in the pocket is in dynamic equilibrium with multiple binding orientations and that the equilibrium is apparently determined by a few critical residues including those at positions 117 and 209.

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