Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse

1995 ◽  
Vol 40 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Wendy Cammer ◽  
H. Zhang ◽  
F. A. Tansey
Keyword(s):  
Carbonic Anhydrase ◽  
Double Mutant ◽  
Mutant Mouse ◽  
Structure And Function ◽  
Carbonic Anhydrase Ii ◽  
And Function ◽  
Myelin Deficient ◽  
Double Mutant Mouse

scholarly journals Rad51c- and Trp53-double-mutant mouse model reveals common features of homologous recombination-deficient breast cancers

Oncogene ◽  
2016 ◽  
Vol 35 (35) ◽  
pp. 4601-4610 ◽  
Author(s):  
M Tumiati ◽  
P M Munne ◽  
H Edgren ◽  
S Eldfors ◽  
A Hemmes ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Mouse Model ◽  
Double Mutant ◽  
Mutant Mouse ◽  
Breast Cancers ◽  
Common Features ◽  
Double Mutant Mouse

scholarly journals Structural Characterization of Carbonic Anhydrase VIII and Effects of Missense Single Nucleotide Variations to Protein Structure and Function

2020 ◽  
Vol 21 (8) ◽  
pp. 2764
Author(s):  
Taremekedzwa Allan Sanyanga ◽  
Özlem Tastan Bishop
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Cross Correlation ◽  
Structure And Function ◽  
The Body ◽  
Conformational Sampling ◽  
Nucleotide Polymorphisms ◽  
Ip3 Receptor ◽  
Single Nucleotide ◽  
And Function

Human carbonic anhydrase 8 (CA-VIII) is an acatalytic isoform of the α -CA family. Though the protein cannot hydrate CO2, CA-VIII is essential for calcium (Ca2+) homeostasis within the body, and achieves this by allosterically inhibiting the binding of inositol 1,4,5-triphosphate (IP3) to the IP3 receptor type 1 (ITPR1) protein. However, the mechanism of interaction of CA-VIII to ITPR1 is not well understood. In addition, functional defects to CA-VIII due to non-synonymous single nucleotide polymorphisms (nsSNVs) result in Ca2+ dysregulation and the development of the phenotypes such as cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (CAMRQ3). The pathogenesis of CAMRQ3 is also not well understood. The structure and function of CA-VIII was characterised, and pathogenesis of CAMRQ3 investigated. Structural and functional characterisation of CA-VIII was conducted through SiteMap and CPORT to identify potential binding site residues. The effects of four pathogenic nsSNVs, S100A, S100P, G162R and R237Q, and two benign S100L and E109D variants on CA-VIII structure and function was then investigated using molecular dynamics (MD) simulations, dynamic cross correlation (DCC) and dynamic residue network (DRN) analysis. SiteMap and CPORT analyses identified 38 unique CA-VIII residues that could potentially bind to ITPR1. MD analysis revealed less conformational sampling within the variant proteins and highlighted potential increases to variant protein rigidity. Dynamic cross correlation (DCC) showed that wild-type (WT) protein residue motion is predominately anti-correlated, with variant proteins showing no correlation to greater residue correlation. DRN revealed variant-associated increases to the accessibility of the N-terminal binding site residues, which could have implications for associations with ITPR1, and further highlighted differences to the mechanism of benign and pathogenic variants. SNV presence is associated with a reduction to the usage of Trp37 in all variants, which has implications for CA-VIII stability. The differences to variant mechanisms can be further investigated to understand pathogenesis of CAMRQ3, enhancing precision medicine-related studies into CA-VIII.

Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1753-1768 ◽  
Author(s):  
M.J. Solloway ◽  
E.J. Robertson
Keyword(s):  
Embryonic Development ◽  
Double Mutant ◽  
Structure And Function ◽  
Bmp Signaling ◽  
Cell Populations ◽  
Specific Cell ◽  
Early Embryonic Lethality ◽  
Branchial Arches ◽  
High Conservation ◽  
And Function

Members of the BMP family of signaling molecules display a high conservation of structure and function, and multiple BMPs are often coexpressed in a variety of tissues during development. Moreover, distinct BMP ligands are capable of activating common pathways. Here we describe the coexpression of two members of the 60A subfamily of BMPs, Bmp5 and Bmp7, at a number of different sites in the embryo from gastrulation onwards. Previous studies demonstrate that loss of either Bmp5 or Bmp7 has negligible effects on development, suggesting these molecules functionally compensate for each other at early stages of embryonic development. Here we show this is indeed the case. Thus we find that Bmp5;Bmp7 double mutants die at 10.5 dpc and display striking defects primarily affecting the tissues where these factors are coexpressed. The present analysis also uncovers novel roles for BMP signaling during the development of the allantois, heart, branchial arches, somites and forebrain. Bmp5 and Bmp7 do not appear to be involved in establishing pattern in these tissues, but are instead necessary for the proliferation and maintenance of specific cell populations. These findings are discussed with respect to potential mechanisms underlying cooperative signaling by multiple members of the TGF-beta superfamily.

Lack of the DNA glycosylases MYH and OGG1 in the cancer prone double mutant mouse does not increase mitochondrial DNA mutagenesis

DNA Repair ◽  
2012 ◽  
Vol 11 (3) ◽  
pp. 278-285 ◽  
Author(s):  
Ruth Halsne ◽  
Ying Esbensen ◽  
Wei Wang ◽  
Katja Scheffler ◽  
Rajikala Suganthan ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Double Mutant ◽  
Mutant Mouse ◽  
Dna Glycosylases ◽  
Double Mutant Mouse ◽  
Dna Mutagenesis

Improvement in survival and muscle function in an mdx/utrn−/− double mutant mouse using a human retinal dystrophin transgene

2006 ◽  
Vol 16 (3) ◽  
pp. 192-203 ◽  
Author(s):  
Roger Gaedigk ◽  
Douglas J. Law ◽  
Kathleen M. Fitzgerald-Gustafson ◽  
Steven G. McNulty ◽  
Ndona N. Nsumu ◽  
...  
Keyword(s):  
Muscle Function ◽  
Double Mutant ◽  
Mutant Mouse ◽  
Improvement In Survival ◽  
Double Mutant Mouse
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