Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis
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Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis. / Aherrahrou, Zouhair; Schlossarek, Saskia; Stoelting, Stephanie; Klinger, Matthias; Geertz, Birgit; Weinberger, Florian; Kessler, Thorsten; Aherrahou, Redouane; Moreth, Kristin; Bekeredjian, Raffi; Hrabě de Angelis, Martin; Just, Steffen; Rottbauer, Wolfgang; Eschenhagen, Thomas; Schunkert, Heribert; Carrier, Lucie; Erdmann, Jeanette.
in: BASIC RES CARDIOL, Jahrgang 111, Nr. 1, 2016, S. 6-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Knock-out of nexilin in mice leads to dilated cardiomyopathy and endomyocardial fibroelastosis
AU - Aherrahrou, Zouhair
AU - Schlossarek, Saskia
AU - Stoelting, Stephanie
AU - Klinger, Matthias
AU - Geertz, Birgit
AU - Weinberger, Florian
AU - Kessler, Thorsten
AU - Aherrahou, Redouane
AU - Moreth, Kristin
AU - Bekeredjian, Raffi
AU - Hrabě de Angelis, Martin
AU - Just, Steffen
AU - Rottbauer, Wolfgang
AU - Eschenhagen, Thomas
AU - Schunkert, Heribert
AU - Carrier, Lucie
AU - Erdmann, Jeanette
PY - 2016
Y1 - 2016
N2 - Cardiomyopathy is one of the most commoncauses of chronic heart failure worldwide. Mutations inthe gene encoding nexilin (NEXN) occur in patients withboth hypertrophic and dilated cardiomyopathy (DCM);however, little is known about the pathophysiologicalmechanisms and relevance of NEXN to these disorders.Here, we evaluated the functional role of NEXN using aconstitutive Nexn knock-out (KO) mouse model.Heterozygous (Het) mice were inter-crossed to producewild-type (WT), Het, and homozygous KO mice. At birth,32, 46, and 22 % of the mice were WT, Het, and KO,respectively, which is close to the expected Mendelianratio. After postnatal day 6, the survival of the Nexn KOmice decreased dramatically and all of the animals diedby day 8. Phenotypic characterizations of the WT and KOmice were performed at postnatal days 1, 2, 4, and 6. Atbirth, the relative heart weights of the WT and KO micewere similar; however, at day 4, the relative heart weightof the KO group was 2.3-fold higher than of the WTgroup. In addition, the KO mice developed rapidly progressivecardiomyopathy with left ventricular dilation andwall thinning and decreased cardiac function. At day 6,the KO mice developed a fulminant DCM phenotypecharacterized by dilated ventricular chambers and systolicdysfunction. At this stage, collagen deposits and someelastin deposits were observed within the left ventriclecavity, which resembles the features of endomyocardialfibroelastosis (EFE). Overall, these results furtheremphasize the role of NEXN in DCM and suggest a novelrole in EFE.
AB - Cardiomyopathy is one of the most commoncauses of chronic heart failure worldwide. Mutations inthe gene encoding nexilin (NEXN) occur in patients withboth hypertrophic and dilated cardiomyopathy (DCM);however, little is known about the pathophysiologicalmechanisms and relevance of NEXN to these disorders.Here, we evaluated the functional role of NEXN using aconstitutive Nexn knock-out (KO) mouse model.Heterozygous (Het) mice were inter-crossed to producewild-type (WT), Het, and homozygous KO mice. At birth,32, 46, and 22 % of the mice were WT, Het, and KO,respectively, which is close to the expected Mendelianratio. After postnatal day 6, the survival of the Nexn KOmice decreased dramatically and all of the animals diedby day 8. Phenotypic characterizations of the WT and KOmice were performed at postnatal days 1, 2, 4, and 6. Atbirth, the relative heart weights of the WT and KO micewere similar; however, at day 4, the relative heart weightof the KO group was 2.3-fold higher than of the WTgroup. In addition, the KO mice developed rapidly progressivecardiomyopathy with left ventricular dilation andwall thinning and decreased cardiac function. At day 6,the KO mice developed a fulminant DCM phenotypecharacterized by dilated ventricular chambers and systolicdysfunction. At this stage, collagen deposits and someelastin deposits were observed within the left ventriclecavity, which resembles the features of endomyocardialfibroelastosis (EFE). Overall, these results furtheremphasize the role of NEXN in DCM and suggest a novelrole in EFE.
M3 - SCORING: Journal article
VL - 111
SP - 6
EP - 6
JO - BASIC RES CARDIOL
JF - BASIC RES CARDIOL
SN - 0300-8428
IS - 1
ER -