Ankyrin-B Syndrome: Enhanced Cardiac Function Balanced by Risk of Cardiac Death and Premature Senescence
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{"title"=>"Ankyrin-B syndrome: Enhanced cardiac function balance by risk of cardiac death and premature senescence", "type"=>"journal", "authors"=>[{"first_name"=>"Peter J.", "last_name"=>"Mohler", "scopus_author_id"=>"7004029119"}, {"first_name"=>"Jane A.", "last_name"=>"Healy", "scopus_author_id"=>"23049926100"}, {"first_name"=>"Hui", "last_name"=>"Xue", "scopus_author_id"=>"35082934000"}, {"first_name"=>"Annibale A.", "last_name"=>"Puca", "scopus_author_id"=>"7004234433"}, {"first_name"=>"Crystal F.", "last_name"=>"Kline", "scopus_author_id"=>"14323491500"}, {"first_name"=>"R. Rand", "last_name"=>"Allingham", "scopus_author_id"=>"7004193048"}, {"first_name"=>"Evangelia G.", "last_name"=>"Kranias", "scopus_author_id"=>"35479209700"}, {"first_name"=>"Howard A.", "last_name"=>"Rockman", "scopus_author_id"=>"35518621200"}, {"first_name"=>"Vann", "last_name"=>"Bennett", "scopus_author_id"=>"7101915268"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"17940615", "doi"=>"10.1371/journal.pone.0001051", "sgr"=>"38049084008", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "scopus"=>"2-s2.0-38049084008", "issn"=>"19326203", "pui"=>"351560117"}, "id"=>"43492286-1e43-35de-ad63-a54925bc7faa", "abstract"=>"Here we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants. The prevalence of certain ANK2 (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and in vitro phenotypes were unexpectedly common. Studies with the ankyrin-B +/- mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term \"ankyrin-B syndrome\", which may contribute to both aging-related disorders and enhanced cardiac function. © 2007 Mohler et al.", "link"=>"http://www.mendeley.com/research/ankyrinb-syndrome-enhanced-cardiac-function-balance-risk-cardiac-death-premature-senescence", "reader_count"=>3, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/464681", "https://ndownloader.figshare.com/files/464696", "https://ndownloader.figshare.com/files/464722"], "description"=>"<div><p>Here we report the unexpected finding that specific human <em>ANK2</em> variants represent a new example of balanced human variants. The prevalence of certain <em>ANK2</em> (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and <em>in vitro</em> phenotypes were unexpectedly common. Studies with the ankyrin-B<sup>+/−</sup> mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term “ankyrin-B syndrome”, which may contribute to both aging-related disorders and enhanced cardiac function.</p></div>", "links"=>[], "tags"=>["ankyrin-b", "enhanced", "cardiac", "premature", "senescence"], "article_id"=>151590, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.s001", "https://dx.doi.org/10.1371/journal.pone.0001051.s002", "https://dx.doi.org/10.1371/journal.pone.0001051.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Ankyrin_B_Syndrome_Enhanced_Cardiac_Function_Balanced_by_Risk_of_Cardiac_Death_and_Premature_Senescence/151590", "title"=>"Ankyrin-B Syndrome: Enhanced Cardiac Function Balanced by Risk of Cardiac Death and Premature Senescence", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-10-17 00:26:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/943985"], "description"=>"<p>A. The domain structure of 220 kD ankyrin-B protein, showing the N-terminal membrane binding domain (red), spectrin-binding domain (green), death domain (yellow), and C-terminal domain (blue). Magnified insert shows the location of previously identified variants. Variants had range of functional severity in mouse cardiomyocytes, indicated with yellow (mild), gray (moderate) or red (severe) bars. B. Affected residues are highly conserved across species. Ankyrin-B alignment from human, monkey, rat, mouse, dog, chicken, and zebrafish. Residues affected by the nucleotide variants are shown in red. C. Allele frequency of the <i>ANK2</i> variants in 1152 Europeans (black bars) and 384 West Africans (red bars) as determined by PCR based allelic discrimination assay. Right, Allele frequency of pooled functional variants. D. Ankyrin-B variants are less frequent in Europeans that reach the age of 100. Allele frequency of the each variant in European non-centenarians (black bars) and centenarians (red bars). Asterisks indicate that no individuals were identified with the variant.</p>", "links"=>[], "tags"=>["ankyrin-b", "variants", "distributions", "populations"], "article_id"=>614367, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_ankyrin_B_gene_variants_have_unique_distributions_in_distinct_ethnic_populations_and_may_affect_longevity_/614367", "title"=>"Human ankyrin-B gene variants have unique distributions in distinct ethnic populations and may affect longevity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-10-17 01:12:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/944039"], "description"=>"<p>(A) Isolated unloaded ankyrin-B<sup>+/−</sup> ventricular cardiomyocytes display increased cellular shortening compared to unloaded WT cardiomyocytes, consistent with increased [Ca<sup>2+</sup>]<sub>i</sub> transients <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001051#pone.0001051-Mohler3\" target=\"_blank\">[14]</a>. Asterisk represents p<0.01 between untreated WT and ankyrin-B<sup>+/−</sup> cardiomyocytes (15–20 cardiomyocytes from 4–5 mice). WT and ankyrin-B<sup>+/−</sup> cardiomyocytes treated with maximal doses of ouabain (100 µM) display significant elevations in cellular shortening compared with untreated WT and ankyrin-B<sup>+/−</sup> cardiomyocytes (15–20 cardiomyocytes from 4–5 mice, p<0.01, asterisks). (B–C) Live, isolated ankyrin-B<sup>+/−</sup> cardiomyocytes display reduced (∼20%) surface expression as measured by binding of [<sup>3</sup>H]-ouabain (n = 3, p<0.01). (D–E) Conscious echocardiograms of wild-type and ankyrin-B<sup>+/−</sup> mice before and after transverse aortic constriction. Black labels represent wild-type animals, white labels represent ankyrin-B<sup>+/−</sup> data. Ankyrin-B<sup>+/−</sup> mice show preserved fractional shortening compared to wild-type mice over a wide range of hemodynamic stress (induced through transverse aortic constriction).</p>", "links"=>[], "tags"=>["ankyrin-b-dependent", "sites", "mimics", "cellular"], "article_id"=>614424, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_ankyrin_B_dependent_3_H_ouabain_binding_sites_mimics_the_cellular_action_of_digitalis_/614424", "title"=>"Loss of ankyrin-B-dependent [<sup>3</sup>H]-ouabain-binding sites mimics the cellular action of digitalis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-10-17 01:13:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/944191"], "description"=>"<p>Wild-type (n = 8) and ankyrin-B<sup>+/−</sup> mice (n = 8), and wild-type (n = 10) and phospholamban-null mice (n = 10) were surgically-implanted with radiotelemetry ECG probes. Mice were injected with a high dose (10 mg/kg) of ouabain or 2 mg/kg epinephrine, and conscious ECGs were recorded. Unlike wild-type or phospholamban-null mice, ankyrin-B<sup>+/−</sup> mice display resistance to ouabain-induced ventricular arrhythmia (1/8) and death (0/8). Panel A represents ECG data from wild-type, ankyrin-B<sup>+/−</sup>, and PLN null mice treated with ouabain. Data in panels B–D represent summary syncope, death, and arrhythmia data for mice following exercise (panel B), exercise plus epinephrine injection (panel C), and ouabain injection (panel D).</p>", "links"=>[], "tags"=>["mice", "resistant", "ouabain-induced", "ventricular", "arrhythmia"], "article_id"=>614570, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ankyrin_B_8722_mice_are_resistant_to_ouabain_induced_ventricular_arrhythmia_and_death_/614570", "title"=>"Ankyrin-B<sup>+/−</sup> mice are resistant to ouabain-induced ventricular arrhythmia and death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-10-17 01:16:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/944304"], "description"=>"<p>Gross phenotypes of wild-type and ankyrin-B<sup>+/−</sup> mice at (A) eight weeks, (B) six months, and C) two years. While we observe no major differences in phenotypes at eight weeks, we observe a slight decrease in size and the presence of lordokyphosis in ankyrin-B<sup>+/−</sup> mice at six months of age. At two years, unlike wild-type littermates, living ankyrin-B<sup>+/−</sup> mice display a significant decrease in adiposity and loss of soft tissues as well as prominent lordokyphosis. D, Dorsal hair regrowth phenotypes in 12 month C57Bl/6 wild-type and ankyrin-B<sup>+/−</sup> littermates. We observed no difference in regrowth in 1 or 3 month mice. E, H&E stain of dorsal skin sections from age-matched (24 month) wild-type and ankyrin-B<sup>+/−</sup> littermates. Note the decrease in adipose from the subdermis of ankyrin-B<sup>+/−</sup> mouse skin. F, Reduced longevity of ankyrin-B<sup>+/−</sup> mice compared with wild-type littermates.</p>", "links"=>[], "tags"=>["mice", "premature", "senescence", "reduced"], "article_id"=>614684, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ankyrin_B_8722_mice_display_premature_senescence_and_reduced_longevity_/614684", "title"=>"Ankyrin-B<sup>+/−</sup> mice display premature senescence and reduced longevity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-10-17 01:18:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/944450"], "description"=>"<p>A, Relative 220 kD ankyrin-B expression across mouse tissues. Right panel illustrates expression of 220 kD ankyrin-B in ankyrin-B<sup>+/−</sup> mouse tissues compared with wild-type littermate tissue (n>3, p<0.05). B, Quantitative immunoblot of 220 kD ankyrin-B expression in wild-type and ankyrin-B<sup>+/−</sup> mouse pancreas using ankyrin-B Ig. Protein levels were quantified by 125-labeled Protein A (n>3). C–D, Immunolocalization of glucagon (left) and ankyrin-B (right) in the Islet of wild-type mouse pancreas. Note that we observe no immunoreactivity of ankyrin-B in the exocrine pancreas. E, Immunolocalization of somatostatin and ankyrin-B in wild-type islets. We observe no co-expression of ankyrin-B and somatostatin in delta cells. F, Immunolocalization of glucagon and ankyrin-B in wild-type mouse islets. We observe no co-localization of glucagon and ankyrin-B in alpha cells. G, Immunolocalization of glucagon and ankyrin-B in Islets of ankyrin-B<sup>+/−</sup> mice. Note the significant decrease in ankyrin-B levels.</p>", "links"=>[], "tags"=>["biochemistry/cell signaling and trafficking structures", "genetics and genomics/disease models", "cardiovascular disorders/arrhythmias, electrophysiology, and pacing"], "article_id"=>614828, "categories"=>["Biochemistry", "Medicine", "Genetics"], "users"=>["Peter J. Mohler", "Jane A. Healy", "Hui Xue", "Annibale A. Puca", "Crystal F. Kline", "R. Rand Allingham", "Evangelia G. Kranias", "Howard A. Rockman", "Vann Bennett"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001051.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ankyrin_B_haploinsufficiency_in_multiple_cell_types_/614828", "title"=>"Ankyrin-B-haploinsufficiency in multiple cell types.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-10-17 01:20:28"}

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Relative Metric

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