1. Primary Cilia Deletion in Pancreatic Epithelial Cells Results in Cyst Formation and Pancreatitis 
David A. Cano, Shigeki Sekine, Matthias Hebrok 
Gastroenterology 
Volume 131, Issue 6, Pages (December 2006)
DOI: /j.gastro
Copyright © 2006 AGA Institute Terms and Conditions

2. Figure 1
Anatomic and histologic analysis of the pathology in Pdx1-Creearly;Kif3alox/lox mice. Loss of acini architecture is observed after birth (P2) in Pdx1-Creearly;Kif3alox/lox mice (B) compared with control mice (A). Note the increase of interstitial cells in lobules of Pdx1-Creearly;Kif3alox/lox pancreas. Arrows in B indicate acini displaying enlarged lumen. (C and D) Gross pancreatic morphology in control mice (C) and Pdx1-Creearly;Kif3alox/lox mice displaying dilation of the ducts (D, arrowheads) at P15. (E and F) Progressive acinar cell loss and ductal dilation increase in Pdx1-Creearly;Kif3alox/lox mice with age.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

3. Figure 2
Ductal cell expansion and cilia loss in Pdx1-Creearly;Kif3alox/lox mice. In control pancreatic sections (A), cilia are easily observed in islets and ducts (inset). A dramatic decrease in cilia number is detected in Pdx1-Creearly;Kif3alox/lox mice at P15 (B) in both islets and ducts (inset). Cilia were visualized using an antibody against acetylated tubulin, a protein that is preferentially localized in the ciliary axoneme. A dramatic ductal dilation in Pdx1-Creearly;Kif3alox/lox mice is observed at P7 in all pancreatic ducts, including interlobular (iel), intralobular (ial), and intercalated ducts (ic) (D). Ducts are normal in control mice (C). In P15 Pdx1-Creearly;Kif3alox/lox mice, extensive acinar cell loss occurs as shown by the decrease of amylase staining and increased dilation of duct-like structures marked by lectin DBA staining (F). An area of transition is seen with metaplasia of acinar tissue to ductal phenotype (outlined in white). Note the absence of cells coexpresing acinar and ductal markers. Control mice show normal acinar and ductal architecture (E).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

4. Figure 3
Extracellular matrix abnormalities in Pdx1-Creearly;Kif3alox/lox mice. (A and B) Gomori trichrome staining (blue) reveals significant increase in collagen deposition in the periductal region of Pdx1-Creearly;Kif3alox/lox pancreas when compared with control tissue at P15. Note the presence of dilated ducts (asterisks). (C) Quantitative mRNA analysis indicates up-regulation of TGF-β ligands (TGF-β2 and TGF-β3) and target genes (Ctgf) in Pdx1-Creearly;Kif3alox/lox mice compared with control littermates at P7 (P < .01). (D) Quantitative mRNA analysis indicates up-regulation of MMP-7, Timp-1, and Timp-4 expression in Pdx1-Creearly;Kif3alox/lox mice compared with control littermates at P7 (P < .01). Expression of pancreas genes was compared with the expression level of β-glucuronidase (GUS).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

5. Figure 4
Increased acinar cell loss and ductal cell expansion in Pdx1-Creearly;Kif3alox/lox mice. TUNEL staining shows an increase of apoptotic cells in pancreas of Pdx1-Creearly;Kif3alox/lox mice (B, arrowheads) when compared with control mice (A). Staining of E17.5 Pdx1-Creearly;Kif3alox/lox pancreatic tissue with mucin demonstrates ductal dilation in both intercalated ducts (arrowheads) and intralobular ducts (D, arrows) compared with control mice (C). Pdx1-Creearly;Kif3alox/lox mice exhibit increased proliferation in the exocrine compartment as shown by phospho-Histone H3 staining (F, arrowheads) compared with control littermates (E).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

6. Figure 5
Absence of pancreatic phenotypes in Pdx1-Crelate;Kif3alox/lox mice. Histologic analysis reveals no pancreatic abnormalities in 1-month-old Pdx1-Crelate;Kif3alox/lox mice (B) compared with control littermates (A). (C) Cilia are present in ducts and islets in control mice. (D) In Pdx1-Crelate;Kif3alox/lox mice, cilia number in islets is decreased but not in ducts. Islets (i) are outlined in white for better visualization.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

7. Figure 6
Analysis of adult Pdx1-Creearly;Kif3alox/lox mice. Gross morphology of Pdx1-Creearly;Kif3alox/lox pancreas showing translucent appearance (B) compared with control mice (A). Histologic analysis reveals accumulation of adipose tissue within the exocrine pancreas in 3-month-old Pdx1-Creearly;Kif3alox/lox mice (D). Control littermates show little adipose tissue (C). Arrow in C indicates peripancreatic fat depots. Arrowhead in D indicates an islet located among adipose tissue. The islet architecture of 3-month-old Pdx1-Creearly;Kif3alox/lox mice (E) is comparable with controls (F) as revealed by glucagon (red) and insulin (green) staining of pancreas sections. DAPI-stained nuclei are shown in blue. Glucose tolerance tests performed in 3-month-old mice showed normal β-cell function in Pdx1-Creearly;Kif3alox/lox mice (G, control mice, red, n = 5; Kif3a mutant mice, black, n = 5). Error bars represent SEM. du, duodenum; p, pancreas.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

8. Figure 7
Pancreatic abnomalities in aged Pdx1-Creearly;Kif3alox/lox mice. Pancreatic gross morphology of control mice (A) and 3 classes of 12-month-old Pdx1-Creearly;Kif3alox/lox mice (B–D). Mutants were grouped based on different pancreatic lesions, including severe adhesion (B), elaborate cysts (C), and smaller cysts with severe ductal dilation (D). Histologic analysis of Pdx1-Creearly;Kif3alox/lox mice shows severe fibrosis associated with inflammatory cell infiltration (F; and in higher magnification, J), cystic structures (G; and in higher magnification, K), and extensive ductal dilation (H; and in higher magnification, L). Normal areas of acinar tissue (a) are found in Pdx1-Creearly;Kif3alox/lox mice. No pancreatic abnormalities are observed in control littermates (E; and in higher magnification, I). Boxes in E, F, G, and H mark the areas that are shown in higher magnification in I, J, K, and L, respectively. Asterisks indicate dilated ducts. A normal duct (d) is shown in I. Arrows in J and L indicate the presence of inflammatory cells. d, duodenum; p, pancreas; s, stomach; sp, spleen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions

9. Figure 8
Ductal cell lesions in aged Pdx1-Creearly;Kif3alox/lox mice. Eosinophilic ductal metaplasia is observed in 12-month-old Pdx1-Creearly;Kif3alox/lox mice (B). Compare eosinophilic ductal cells (arrowhead) with normal ductal cells (arrow). Normal duct (d) and islet (i) are shown in A. Increased phospho-ERK expression is found in ducts of 12-month-old Pdx1-Creearly;Kif3alox/lox mice (D, arrow) but not adjacent acinar cells (arrowhead). Strong phospho-ERK staining in control mice is limited to blood vessels (outlined) and a few islet cells (i) in control mice (C). Note the absence of significant phospho-ERK staining in ducts (arrow).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2006 AGA Institute Terms and Conditions