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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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Related in: MedlinePlus

Enlarged intestines and atrophy of exocrine pancreas in cKO mice.(A, B) Necropsy of tamoxifen-treated F/F;Cre (cKO) and F/F controls (Ctrl) revealed enlarged intestines (A) and a dramatic reduction in the size of pancreas (B) in cKO animals. Analysis was repeated >30 times. (C). Histology of pancreata tissue harvested two weeks after the last tamoxifen administration from F/F control (Ctrl) and F/F;Cre (cKO) animals. (i, ii) Control animals displayed an organized structure of exocrine pancreas (Exo) with interspersed Islets of Langerhans (L). Acinar cells were polarized with more basophilic staining (blue) corresponding to endoplasmic reticulum and accumulation of secretory granules at the apical side. (ii) is a magnification of the boxed area indicated in (i). (iii–v) Pancreas of cKO mice displayed atrophy of exocrine pancreas, enrichment of adipose tissue and apparently normal Islets of Langerhans (L). Only small parts of normal exocrine pancreas could be found (Exo). The acinar cells were replaced by duct-like tubular complexes (T). (v) is a magnification of the boxed area indicated in (iv). Scale bar = 100 µm.
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pone-0020203-g004: Enlarged intestines and atrophy of exocrine pancreas in cKO mice.(A, B) Necropsy of tamoxifen-treated F/F;Cre (cKO) and F/F controls (Ctrl) revealed enlarged intestines (A) and a dramatic reduction in the size of pancreas (B) in cKO animals. Analysis was repeated >30 times. (C). Histology of pancreata tissue harvested two weeks after the last tamoxifen administration from F/F control (Ctrl) and F/F;Cre (cKO) animals. (i, ii) Control animals displayed an organized structure of exocrine pancreas (Exo) with interspersed Islets of Langerhans (L). Acinar cells were polarized with more basophilic staining (blue) corresponding to endoplasmic reticulum and accumulation of secretory granules at the apical side. (ii) is a magnification of the boxed area indicated in (i). (iii–v) Pancreas of cKO mice displayed atrophy of exocrine pancreas, enrichment of adipose tissue and apparently normal Islets of Langerhans (L). Only small parts of normal exocrine pancreas could be found (Exo). The acinar cells were replaced by duct-like tubular complexes (T). (v) is a magnification of the boxed area indicated in (iv). Scale bar = 100 µm.

Mentions: Littermates of F/F;Cre (cKO, n>30) and F/F controls (Ctrl, n>30) were treated with tamoxifen. Necropsy one week after the last tamoxifen administration revealed major macroscopic changes in the intestinal system and pancreas (Figs. 4A and B). The intestine of all cKO animals analyzed was dilated (Fig. 4A). The overall length of the gastrointestinal tract was not affected (data not shown). In addition, the pancreas was found to be dramatically smaller in all cKO mice compared to the controls (Fig. 4B). Interestingly, cKO mice analyzed up to 18 months after the last tamoxifen injection maintained the dilated intestines and the pancreatic atrophy indicating that these effects were irreversible. No polyps or tumors were found.


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)

Enlarged intestines and atrophy of exocrine pancreas in cKO mice.(A, B) Necropsy of tamoxifen-treated F/F;Cre (cKO) and F/F controls (Ctrl) revealed enlarged intestines (A) and a dramatic reduction in the size of pancreas (B) in cKO animals. Analysis was repeated >30 times. (C). Histology of pancreata tissue harvested two weeks after the last tamoxifen administration from F/F control (Ctrl) and F/F;Cre (cKO) animals. (i, ii) Control animals displayed an organized structure of exocrine pancreas (Exo) with interspersed Islets of Langerhans (L). Acinar cells were polarized with more basophilic staining (blue) corresponding to endoplasmic reticulum and accumulation of secretory granules at the apical side. (ii) is a magnification of the boxed area indicated in (i). (iii–v) Pancreas of cKO mice displayed atrophy of exocrine pancreas, enrichment of adipose tissue and apparently normal Islets of Langerhans (L). Only small parts of normal exocrine pancreas could be found (Exo). The acinar cells were replaced by duct-like tubular complexes (T). (v) is a magnification of the boxed area indicated in (iv). Scale bar = 100 µm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3108585&req=5

pone-0020203-g004: Enlarged intestines and atrophy of exocrine pancreas in cKO mice.(A, B) Necropsy of tamoxifen-treated F/F;Cre (cKO) and F/F controls (Ctrl) revealed enlarged intestines (A) and a dramatic reduction in the size of pancreas (B) in cKO animals. Analysis was repeated >30 times. (C). Histology of pancreata tissue harvested two weeks after the last tamoxifen administration from F/F control (Ctrl) and F/F;Cre (cKO) animals. (i, ii) Control animals displayed an organized structure of exocrine pancreas (Exo) with interspersed Islets of Langerhans (L). Acinar cells were polarized with more basophilic staining (blue) corresponding to endoplasmic reticulum and accumulation of secretory granules at the apical side. (ii) is a magnification of the boxed area indicated in (i). (iii–v) Pancreas of cKO mice displayed atrophy of exocrine pancreas, enrichment of adipose tissue and apparently normal Islets of Langerhans (L). Only small parts of normal exocrine pancreas could be found (Exo). The acinar cells were replaced by duct-like tubular complexes (T). (v) is a magnification of the boxed area indicated in (iv). Scale bar = 100 µm.
Mentions: Littermates of F/F;Cre (cKO, n>30) and F/F controls (Ctrl, n>30) were treated with tamoxifen. Necropsy one week after the last tamoxifen administration revealed major macroscopic changes in the intestinal system and pancreas (Figs. 4A and B). The intestine of all cKO animals analyzed was dilated (Fig. 4A). The overall length of the gastrointestinal tract was not affected (data not shown). In addition, the pancreas was found to be dramatically smaller in all cKO mice compared to the controls (Fig. 4B). Interestingly, cKO mice analyzed up to 18 months after the last tamoxifen injection maintained the dilated intestines and the pancreatic atrophy indicating that these effects were irreversible. No polyps or tumors were found.

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