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Multiple phenotypes in adult mice following inactivation of the Coxsackievirus and Adenovirus Receptor (Car) gene.

Pazirandeh A, Sultana T, Mirza M, Rozell B, Hultenby K, Wallis K, Vennström B, Davis B, Arner A, Heuchel R, Löhr M, Philipson L, Sollerbrant K - PLoS ONE (2011)

Bottom Line: To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR), a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues.All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia.These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institutet for Cancer Research, Stockholm Branch, Stockholm, Sweden.

ABSTRACT
To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR), a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

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Atrioventricular heart block and ultrastructural changes in hearts of cKO mice.(A) Representative ECG recordings of tamoxifen-treated F/F control (Ctrl, upper panel) and F/F;Cre (cKO, lower panel) animals. A complete AV block was demonstrated in the cKO animals while control mice showed normal sinus rhythm. Arrows mark the individual P waves. Note the absence of a constant coupling interval between the P waves and the QRS complexes in cKO mice. (B) Transmission electron microscopy of cardiac muscle from tamoxifen-treated F/F control (Ctrl) and F/F;Cre (cKO) animals. A disconnection between myofilaments and big vacuoles containing parts of membranes (arrows) and wider zonula adherens containing a clot like contents (arrow heads) was observed in cKO animals. The experiment was performed on three different animals from each group. Scale bar = 1 µm.
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pone-0020203-g005: Atrioventricular heart block and ultrastructural changes in hearts of cKO mice.(A) Representative ECG recordings of tamoxifen-treated F/F control (Ctrl, upper panel) and F/F;Cre (cKO, lower panel) animals. A complete AV block was demonstrated in the cKO animals while control mice showed normal sinus rhythm. Arrows mark the individual P waves. Note the absence of a constant coupling interval between the P waves and the QRS complexes in cKO mice. (B) Transmission electron microscopy of cardiac muscle from tamoxifen-treated F/F control (Ctrl) and F/F;Cre (cKO) animals. A disconnection between myofilaments and big vacuoles containing parts of membranes (arrows) and wider zonula adherens containing a clot like contents (arrow heads) was observed in cKO animals. The experiment was performed on three different animals from each group. Scale bar = 1 µm.

Mentions: ECG was performed 24 weeks (cKO, n = 10; littermate controls, n = 5) after the last tamoxifen administration. In each animal, at least 30 seconds of ECG recording was examined. All control mice exhibited sinus rhythm, without ectopic beats, and with a mean heart rate of 549±25 min−1 (mean ± SD, n = 5, range = 478–589), and a mean PQ interval (measured from the start of the P wave to the beginning of the Q wave) of 38±5 (mean ± SD, n = 5, range 32–49 ms) milliseconds. All examined cKO mice showed a complete atrioventricular (AV) block with temporal dissociation between atrial depolarisation (P waves) and ventricular depolarisation (QRS complexes). Figure 5A shows representative tracings from a control mouse (top panel) and a cKO mouse (bottom panel). The cKO mice showed an average P-wave frequency of 479±133 min−1 (mean ± SD, n = 10, range = 248–644), and an average R-wave frequency of 580±47 min−1 (mean±SD, n = 10, range = 527–656). The P-wave frequency was significantly slower than the R-wave frequency (P<0.05; Student's t-test). The ventricular frequency in cKO mice was slightly faster than that of their control counterparts, however this effect was not statistically significant (p = 0.20, unpaired Student's t-test). No major difference in the duration of the QRS complexes was observed between the control and the cKO groups.


Multiple phenotypes in adult mice following inactivation of the Coxsackievirus and Adenovirus Receptor (Car) gene.

Pazirandeh A, Sultana T, Mirza M, Rozell B, Hultenby K, Wallis K, Vennström B, Davis B, Arner A, Heuchel R, Löhr M, Philipson L, Sollerbrant K - PLoS ONE (2011)

Atrioventricular heart block and ultrastructural changes in hearts of cKO mice.(A) Representative ECG recordings of tamoxifen-treated F/F control (Ctrl, upper panel) and F/F;Cre (cKO, lower panel) animals. A complete AV block was demonstrated in the cKO animals while control mice showed normal sinus rhythm. Arrows mark the individual P waves. Note the absence of a constant coupling interval between the P waves and the QRS complexes in cKO mice. (B) Transmission electron microscopy of cardiac muscle from tamoxifen-treated F/F control (Ctrl) and F/F;Cre (cKO) animals. A disconnection between myofilaments and big vacuoles containing parts of membranes (arrows) and wider zonula adherens containing a clot like contents (arrow heads) was observed in cKO animals. The experiment was performed on three different animals from each group. Scale bar = 1 µm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3108585&req=5

pone-0020203-g005: Atrioventricular heart block and ultrastructural changes in hearts of cKO mice.(A) Representative ECG recordings of tamoxifen-treated F/F control (Ctrl, upper panel) and F/F;Cre (cKO, lower panel) animals. A complete AV block was demonstrated in the cKO animals while control mice showed normal sinus rhythm. Arrows mark the individual P waves. Note the absence of a constant coupling interval between the P waves and the QRS complexes in cKO mice. (B) Transmission electron microscopy of cardiac muscle from tamoxifen-treated F/F control (Ctrl) and F/F;Cre (cKO) animals. A disconnection between myofilaments and big vacuoles containing parts of membranes (arrows) and wider zonula adherens containing a clot like contents (arrow heads) was observed in cKO animals. The experiment was performed on three different animals from each group. Scale bar = 1 µm.
Mentions: ECG was performed 24 weeks (cKO, n = 10; littermate controls, n = 5) after the last tamoxifen administration. In each animal, at least 30 seconds of ECG recording was examined. All control mice exhibited sinus rhythm, without ectopic beats, and with a mean heart rate of 549±25 min−1 (mean ± SD, n = 5, range = 478–589), and a mean PQ interval (measured from the start of the P wave to the beginning of the Q wave) of 38±5 (mean ± SD, n = 5, range 32–49 ms) milliseconds. All examined cKO mice showed a complete atrioventricular (AV) block with temporal dissociation between atrial depolarisation (P waves) and ventricular depolarisation (QRS complexes). Figure 5A shows representative tracings from a control mouse (top panel) and a cKO mouse (bottom panel). The cKO mice showed an average P-wave frequency of 479±133 min−1 (mean ± SD, n = 10, range = 248–644), and an average R-wave frequency of 580±47 min−1 (mean±SD, n = 10, range = 527–656). The P-wave frequency was significantly slower than the R-wave frequency (P<0.05; Student's t-test). The ventricular frequency in cKO mice was slightly faster than that of their control counterparts, however this effect was not statistically significant (p = 0.20, unpaired Student's t-test). No major difference in the duration of the QRS complexes was observed between the control and the cKO groups.

Bottom Line: To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR), a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues.All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia.These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institutet for Cancer Research, Stockholm Branch, Stockholm, Sweden.

ABSTRACT
To determine the normal function of the Coxsackievirus and Adenovirus Receptor (CAR), a protein found in tight junctions and other intercellular complexes, we constructed a mouse line in which the CAR gene could be disrupted at any chosen time point in a broad spectrum of cell types and tissues. All knockouts examined displayed a dilated intestinal tract and atrophy of the exocrine pancreas with appearance of tubular complexes characteristic of acinar-to-ductal metaplasia. The mice also exhibited a complete atrio-ventricular block and abnormal thymopoiesis. These results demonstrate that CAR exerts important functions in the physiology of several organs in vivo.

Show MeSH
Related in: MedlinePlus