scholarly journals Mice bearing a targeted mutation of nBmp2 display decreased memory capabilities

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Saroj Dhungel ◽  
Aubrey C Rogers ◽  
Ryan D Cordner ◽  
Jaime L Mayo ◽  
Kevin Steed ◽  
...  
Keyword(s):  
Targeted Mutation

scholarly journals NCOG-38. CLINICAL CHARACTERISTICS OF LOW GRADE GLIOMA PATIENTS WITH NON-CANONICAL IDH1 AND IDH2 MUTATIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii137
Author(s):  
Katherine Peters ◽  
Eric Lipp ◽  
Gloria Broadwater ◽  
James Herndon ◽  
Margaret Johnson ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Point Mutations ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Targeted Mutation ◽  
Kaplan Meier ◽  
Idh1 And Idh2 Mutations

Abstract BACKGROUND Low grade gliomas (LGGs) develop in young adults and represent 10-15% of all glial tumors. While LGG patients can have longer survival than higher grade tumors, progression, transformation, and ultimately mortality occurs. Mutations in Isocitrate dehydrogenase 1/2 (IDH1/IDH2) are prevalent in LGG and are responsible for gliomagenesis. The classic IDH1 mutation is located at 132 codon and represented as p.Arg132His, but there are non-canonical IDH1 and IDH2 mutations. We sought to compare clinical characteristics of LGG patients with classic IDH1 p.Arg132His mutation to LGG patients with non-canonical IDH1 and IDH2 mutations. METHODS We queried an IRB-approved registry retrospectively from 12/2004- 9/2019. We included IDH1/IDH2 mutant LGG (WHO grade II) and known IDH1 and IDH2 targeted mutation analysis using standard PCR followed by DNA sequencing to detect point mutations in IDH1/IDH2 genes. We obtained available clinical and histopathological data. We estimated progression-free survival (PFS), time to transformation (TT), and overall survival (OS) using Kaplan-Meier methods. RESULTS We identified 267 LGG patients with median follow-up of 9.1 yrs (95%CI 8.4-9.9 yrs). Classic IDH1 p.Arg132His mutation occurred in 223 (83.9%) patients. IDH2 mutations occurred in 14 (5.2%) patients. Non-canonical IDH1 mutations were in 30 (11.2%) patients and included the following mutations: p.Arg132Cys (13), p.Arg132Gly (10), p.Arg132Ser (4), p.Arg132Leu (1), p.Arg119Gln (1), and p.Arg172Met (1). Initial presentation, OS, and TT did not differ between IDH1/IDH2 groups. PFS differed significantly between groups with improved median PFS in IDH2 mutant LGG (5.4 yrs; 95%CI 3.5-25.2) versus classic IDH1 mutant LGG (4.1 yrs; 95%CI 3.7-4.9 yrs) and non-canonical IDH1 mutant LGG (2.6 yrs; 95%CI 2.1-4.8) (log-rank p=0.019). Notably, non-canonical mutations were more common in astrocytoma (22/30; 73.3%) than other LGG histologies (p=0.018). CONCLUSIONS In this cohort, LGG patients with non-canonical mutations have a shorter time to progression than patients with classic p.Arg132His mutation and IDH2 mutations.

Insufficient VEGFA activity in yolk sac endoderm compromises haematopoietic and endothelial differentiation

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1881-1892 ◽  
Author(s):  
Annette Damert ◽  
Lucile Miquerol ◽  
Marina Gertsenstein ◽  
Werner Risau ◽  
Andras Nagy
Keyword(s):  
Yolk Sac ◽  
Endothelial Differentiation ◽  
Vascular Endothelial ◽  
Visceral Endoderm ◽  
Wild Type ◽  
Hypomorphic Allele ◽  
Targeted Mutation ◽  
Blood Formation ◽  
Opposite Situation ◽  
Endothelial Growth Factor

Vascular endothelial growth factor A (VEGFA) plays a pivotal role in the first steps of endothelial and haematopoietic development in the yolk sac, as well as in the establishment of the cardiovascular system of the embryo. At the onset of gastrulation, VEGFA is primarily expressed in the yolk sac visceral endoderm and in the yolk sac mesothelium. We report the generation and analysis of a Vegf hypomorphic allele, Vegflo. Animals heterozygous for the targeted mutation are viable. Homozygous embryos, however, die at 9.0 dpc because of severe abnormalities in the yolk sac vasculature and deficiencies in the development of the dorsal aortae. We find that providing ‘Vegf wild-type’ visceral endoderm to the hypomorphic embryos restores normal blood and endothelial differentiation in the yolk sac, but does not rescue the phenotype in the embryo proper. In the opposite situation, however, when Vegf hypomorphic visceral endoderm is provided to a wild-type embryo, the ‘Vegf wild-type’ yolk sac mesoderm is not sufficient to support proper vessel formation and haematopoietic differentiation in this extra-embryonic membrane. These findings demonstrate that VEGFA expression in the visceral endoderm is absolutely required for the normal expansion and organisation of both the endothelial and haematopoietic lineages in the early sites of vessel and blood formation. However, normal VEGFA expression in the yolk sac mesoderm alone is not sufficient for supporting the proper development of the early vascular and haematopoietic system.

Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5495-5504 ◽  
Author(s):  
D.M. Supp ◽  
M. Brueckner ◽  
M.R. Kuehn ◽  
D.P. Witte ◽  
L.A. Lowe ◽  
...  
Keyword(s):  
Motor Function ◽  
Single Amino Acid ◽  
Atp Binding ◽  
Amino Acid Difference ◽  
Sequence Classification ◽  
Ciliated Cells ◽  
Targeted Deletion ◽  
Targeted Mutation ◽  
And Function ◽  
Shed Light

Vertebrates develop distinct asymmetries along the left-right axis, which are consistently aligned with the anteroposterior and dorsoventral axes. The mechanisms that direct this handed development of left-right asymmetries have been elusive, but recent studies of mutations that affect left-right development have shed light on the molecules involved. One molecule implicated in left-right specification is left-right dynein (LRD), a microtubule-based motor protein. In the LRD protein of the inversus viscerum (iv) mouse, there is a single amino acid difference at a conserved position, and the lrd gene is one of many genes deleted in the legless (lgl) mutation. Both iv and lgl mice display randomized left-right development. Here we extend the analysis of the lrd gene at the levels of sequence, expression and function. The complete coding sequence of the lrd gene confirms its classification as an axonemal, or ciliary, dynein. Expression of lrd in the node at embryonic day 7.5 is shown to be symmetric. At embryonic day 8.0, however, a striking asymmetric expression pattern is observed in all three germ layers of the developing headfold, suggesting roles in both the establishment and maintenance of left-right asymmetries. At later times, expression of lrd is also observed in the developing floorplate, gut and limbs. These results suggest function for LRD protein in both ciliated and non-ciliated cells, despite its sequence classification as axonemal. In addition, a targeted mutation of lrd was generated that deletes the part of the protein required for ATP binding, and hence motor function. The resulting left-right phenotype, randomization of laterality, is identical to that of iv and lgl mutants. Gross defects in ciliary structure were not observed in lrd/lrd mutants. Strikingly, however, the monocilia on mutant embryonic node cells were immotile. These results prove the identity of the iv and lrd genes. Further, they argue that LRD motor function, and resulting nodal monocilia movement, are required for normal left-right development.

scholarly journals Lack of Skin Fibrosis in Tight Skin (TSK) Mice with Targeted Mutation in the Interleukin-4Rα and Transforming Growth Factor-β Genes

2001 ◽  
Vol 116 (1) ◽  
pp. 136-143 ◽  
Author(s):  
Tracy McGaha ◽  
Shinichiro Saito ◽  
Robert G. Phelps ◽  
Ronald Gordon ◽  
Nancy Noben-Trauth ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Skin Fibrosis ◽  
Tight Skin ◽  
Targeted Mutation

scholarly journals Targeted mutation of SLC4A5 induces arterial hypertension and renal metabolic acidosis

2011 ◽  
Vol 21 (5) ◽  
pp. 1025-1036 ◽  
Author(s):  
Nicole Gröger ◽  
Helga Vitzthum ◽  
Henning Fröhlich ◽  
Marcus Krüger ◽  
Heimo Ehmke ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Arterial Hypertension ◽  
Targeted Mutation

scholarly journals A targeted mutation in Cacng4 exacerbates spike-wave seizures in stargazer (Cacng2) mice

2005 ◽  
Vol 102 (6) ◽  
pp. 2123-2128 ◽  
Author(s):  
V. A. Letts ◽  
C. L. Mahaffey ◽  
B. Beyer ◽  
W. N. Frankel
Keyword(s):  
Targeted Mutation ◽  
Spike Wave

Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2251-2258 ◽  
Author(s):  
A. Mansouri ◽  
A.K. Voss ◽  
T. Thomas ◽  
Y. Yokota ◽  
P. Gruss
Keyword(s):  
Cell Adhesion ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Homeobox Gene ◽  
Axial Skeleton ◽  
Adhesion Properties ◽  
Marker Analysis ◽  
Targeted Mutation ◽  
Differential Cell

The expression of the homeobox gene Uncx4.1 in the somite is restricted to the caudal half of the newly formed somite and sclerotome. Here we show that mice with a targeted mutation of the Uncx4.1 gene exhibit defects in the axial skeleton and ribs. In the absence of Uncx4.1, pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. Histological and marker analysis revealed that Uncx4.1 is not necessary for somite segmentation. It is required to maintain the condensation of the caudal half-sclerotome, from which the missing skeletal elements are derived. The loss of proximal ribs in Pax1/Pax9 double mutants and the data presented here argue for a role of Uncx4.1 upstream of Pax9 in the caudolateral sclerotome. Our results further indicate that Uncx4.1 may be involved in the differential cell adhesion properties of the somite.

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