spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCright, B.
Right arrow Articles by Gridley, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCright, B.
Right arrow Articles by Gridley, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency

Brent McCright, Julie Lozier and Thomas Gridley*

The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA



View larger version (102K):

[in a new window]
  		Fig. 1. J1N2+/– mice exhibit jaundice. Wild-type mouse (bottom) and J1N2+/– double heterozygous littermate (top) at P3. The J1N2+/– mouse exhibits jaundice and growth retardation.

 


View larger version (108K):

[in a new window]
  		Fig. 2. Defects in bile duct differentiation in J1N2+/– mice. (A,B) Hematoxylin and Eosin-stained sections of livers at P8. Bile ducts (arrow,bd) are observed in the portal triads of the wild-type mouse (A), but not in the J1N2+/– mouse (B). (C,D) DBA-stained sections of livers at P6. DBA-positive cells form patent bile ducts (arrow) adjacent to the portal veins in wild-type mice (C). In J1N2+/– mice (D), DBA-positive cells (arrowheads) are present in small numbers adjacent to the portal veins, but these cells have not formed patent ducts. (E,F) WGA-stained sections of livers at P3. No differences in the numbers or distribution of WGA-positive hepatoblasts are observed. (G,H) Hematoxylin and eosin-stained sections of livers of 7-week old adult mice. Bile ducts (arrow) are observed in the portal triads of the wild-type mouse (G). In the J1N2+/– mouse (H), an abnormal proliferation of cells (outlined in yellow) is observed adjacent to the portal vein. bd, bile duct; ha, hepatic artery; pv, portal vein.

 


View larger version (175K):

[in a new window]
  		Fig. 3. Defects in differentiation of bile duct epithelial cells in J1N2+/– and Notch2del1/Notch2del1 mice. (A-D) DBA-stained sections of livers at P0. (A) Wild-type mouse. (B) J1N2+/– littermate of wild-type mouse in A. (C) Wild-type mouse. (D) Notch2del1/Notch2del1 littermate of wild-type mouse in C. Almost no DBA-positive cells (arrows in A and C) are observed in either the J1N2+/– or the Notch2del1/Notch2del1 mice. pv, portal vein.

 


View larger version (104K):

[in a new window]
  		Fig. 4. Heart defects in J1N2+/– mice. (A) Whole-mount preparations of hearts injected with India ink at P3. The J1N2+/– heart (on right) has a narrow pulmonary artery (arrow) and a hypoplastic right ventricle (arrowhead). (B,C) Higher power views of the outflow tracts of the hearts shown in A.

 


View larger version (138K):

[in a new window]
  		Fig. 5. Heart defects in J1N2+/– mice. (A-D) Transverse sections of (A,C) wild-type and (B,D) J1N2+/– hearts at E16.5. (B) Heart with an atrial septal defect (arrow); (D) heart with a ventricular septal defect (arrow). (E,F) Frontal sections of wild-type (E) and J1N2+/– (F) hearts at E15.5. The mutant (F) has a hypoplastic right ventricle and an overriding aorta. ra, right atrium; la, left atrium; ao, aorta; rv, right ventricle; lv, left ventricle.

 


View larger version (152K):

[in a new window]
  		Fig. 6. Expression of Jag1 and Notch2 proteins during bile duct differentiation. (A,B) Immunohistochemistry of sections of livers at P3. (A) Jag1 immunoreactivity is detected in both endothelial cells and non-endothelial supporting cells of portal veins and hepatic arteries. (B) Notch2 immunoreactivity is detected in groups of cells (arrowheads) that appear to be adjacent to the Jag1-expressing cells. (C) Jag1 immunoreactivity is detected in cells surrounding the hepatic arteries and portal veins at P8. (D) The same section as in C, showing DBA immunofluorescence, demonstrates that Jag1 protein is not expressed in bile duct epithelial cells. (E,F) Notch2 immunohistochemistry of sections of livers at E18 of wild-type littermate (E) and Notch2del1/Notch2del1 homozygous mutant (F) embryos. No differences in the numbers or distribution of Notch2-positive cells are observed. Concentrations of Notch2-positive cells adjacent to the developing portal triads are indicated by arrowheads.

 


View larger version (155K):

[in a new window]
  		Fig. 7. Expression of Jag1 and Notch2 proteins in hearts of E13.5 embryos. (A) Jag1 immunoreactivity is present in the pulmonary trunk and the aorta (arrows). Jag1 expression is also observed in cells surrounding the pulmonary trunk. (B) Notch2 protein is highly expressed around the aorta (arrow), in the ventricular myocardium, and at lower levels around the pulmonary trunk. (C) Jag1 immunoreactivity is observed in the pulmonary trunk (arrows) and in coronary vessels (arrowhead). (D) Notch2 is highly expressed in the atrial walls and in ventricular myocardium. All sections are from embryos at E13.5. la, left atrium; ao, aorta; lv, left ventricle; pt, pulmonary trunk; my, myocardium of the left ventricle.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2002