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Unique Liver Lesions of Genetically Altered Mice

The Digitized Atlas of Mouse Liver Lesions

AL-ras x AL-myc Bitransgenic Mouse Liver Lesions - Click on thumbnail to view larger image
An hepatocellular carcinoma in a 6-week old AL-ras x AL-myc bitransgenic mouse.
Hepatocellular Carcinoma
  
Cholangiocarcinoma in a 4-week old AL-ras x AL-myc mouse.
Cholangiocarcinoma
Cholangiocarcinoma
 
 
Hepatitis B Virus Liver Lesions - Click on thumbnails to view larger images

(Images from Chapter 21 of Pathology of Genetically Engineered Mice (2000). JM Ward, JF Mahler, RR Maronpot, JP Sundberg, Eds. with permission of Iowa State University Press, Ames, Iowa)

Gross appearance of a liver with multiple hepatic neoplasms.

Gross Liver
  
Hepatitis B surface antigen in hepatocytes of an HBV transgenic mouse. Immunohistochemistry stain counterstained with hematoxylin.
Hepatocytes
  
Hepatitis B surface antigen is absent in a preneoplastic focus from an HBV transgenic mouse. Immunohistochemistry stain counterstained with hematoxylin.
Preneoplastic focus
  
Hepatocellular adenoma in an HBV transgenic mouse. Arrows indicate compression of adjacent hepatic parenchyma.
Hepatocellular adenoma
  
 
Tg.AC Mouse Liver Lesions: Erythroleukemia - Click on thumbnails to view larger images.

Erythroleukemia is a spontaneous hematopoietic neoplasm of Tg.AC mice characterized by marked hepatomegaly. The affected liver is infiltrated by metarubricytes and less differentiated erythroid precursors.

 

 

Low magnification of erythroleukemic infiltrates in the liver.
Erythroleukemia
  
Erythroleukemic infiltrates in the liver.
Erythroleukemia
  
A higher magnification of hepatic erythroleukemia.
Erythroleukemia
Erythroleukemia
 
 
Tg.AC Mouse Liver Lesions: Myeloproliferative Syndrome (Myelodysplasia) - Click on thumbnails to view larger images.

A spectrum of lesions affecting the liver and other tissues has been observed in Tg.AC mice treated with rotenone. The lesions appear to represent a morphological and biological continuum with varying features of hematopoietic, inflammatory, and neoplastic processes. The cellular infiltrates consist of a mixture of immature and mature myeloid cells and mononuclear cells including plasma cells, often with a striking eosinophil component. The granulocytic infiltrates are often immature and magakarocytes as well as erythropoietic foci may be present. Hyaline degeneration and proliferation of bile ducts has been noted in some cases.

Myelodysplasia with primarily periportal myeloproliferation. Higher magnification shows bridging of cellular infiltrates between portal areas and hyaline degenerative changes in hepatocytes.

Myelodysplasia
Myelodysplasia
Myelodysplasia
Low magnification of severe myeloproliferative infiltration of the liver. Higher magnification shows dense cellular infiltrates and destruction of hepatocytes. A large number of mature eosinophils are evident.
Myeloproliferative infiltration
Myeloproliferative infiltration
Myeloproliferative infiltration_small
Myeloproliferative infiltration_small
  
Another case of myelodysplasia. Numerous granulocytes with eosinophilic granular cytoplasm and a smaller number of mononuclear cells are visible in the high magnification view.
Myelodysplasia
Myelodysplasia
Myelodysplasia
Myelodysplasia
  
Another example of myelodysplasia from a Tg.AC mouse on a FVB background, treated with rotenone.
Myelodysplasia
Myelodysplasia
Myelodysplasia


 
Myelodysplasia
Myelodysplasia
Myelodysplasia
 
AL-TAg Transgenic Mouse Liver Lesions - Click on thumbnails to view larger images
Liver from a 2-week old wild type FVB mouse.
AL-TAg Mouse Liver
  
Liver from a 2-week old AL-TAg transgenic FVB mouse showing increased density of basophilic hepatocytes.
AL-TAg Mouse Liver
  
A transient ductular formation of hepatocytes is seen in liver of this 2-week old AL-TAg mouse.
AL-TAg Mouse Liver
  
Bile duct proliferation in a 4-week old AL-TAg mouse. Some surrounding hepatocytes are dysplastic.
AL-TAg Mouse Liver
  
 
AL-TAg x AL-myc Dual Transgenic Mouse Liver Lesions - Click on thumbnails to view larger images

(The last 12 Images from Chapter 21 of Pathology of Genetically Engineered Mice (2000). JM Ward, JF Mahler, RR Maronpot, JP Sundberg, Eds. with permission of Iowa State University Press, Ames, Iowa)

Ductular formation of hepatocytes in this 2-week old AL-TAg x AL-myc mouse has a predominantly centrilobular localization.

Dual Transgenic Mouse Liver
AL-TAg Mouse Liver
 
An altered hepatocyte focus is arising in an area of ductular formation in this 2-week old AL-TAg x AL-myc mouse.
Dual Transgenic Mouse Liver
  
Focal areas of bile duct proliferation also arise within areas of ductular formation in 2-week old AL-TAg x AL-myc mice.
Dual Transgenic Mouse Liver
  
Increased severity of focal bile duct proliferation associated with an area of ductular formation in a 3-week old AL-TAg x AL-myc mouse.
Dual Transgenic Mouse Liver
  
Areas of ductular formation and bile duct proliferation can be extensive in the livers of 3-week old AL-TAg x AL-myc mice.
Dual Transgenic Mouse Liver
  
By 4-weeks of age much of the liver is replaced by areas of ductular formation, cholangial neoplasms, and hepatocellular neoplasms in AL-TAg x AL-myc mice.
Dual Transgenic Mouse Liver
  
Higher magnification of liver lesions in a 4-week old AL-TAg x AL-myc mouse.
Dual Transgenic Mouse Liver
  
Higher magnification of a well differentiated cholangiocarcinoma in a 4-week old AL-TAg x AL-myc mouse.
Dual Transgenic Mouse Liver
Dual Transgenic Mouse Liver
 
A hepatocellular carcinoma in a 4-week old AL-TAg x AL-myc mouse.
 
Dual Transgenic Mouse Liver
  
Hepatocytomegaly, karyomegaly, and a mitotic figure in a 39- day-old transgenic mouse.
Dual Transgenic Mouse Liverr
  
Bromodeoxyuridine immunohistochemistry from a normal liver showing a low labeling index and from a 39-day-old mouse with a high labeling index.
Dual Transgenic Mouse Liver
  
Basophilic focus in liver of a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
Dual Transgenic Mouse Liver
 
Multiple biliary and hepatocellular hyperplastic and neoplastic lesions in the liver of a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
Confluent biliary and hepatocellular neoplasms totally occupying the left liver lobe of a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
Hepatocellular adenoma and bile duct carcinoma in a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
A proliferative cystic biliary lesion, a solid basophilic adenoma, and a bile duct adenoma in a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
Juxtaposition of a bile duct adenocarcinoma and a hepatocellular adenoma in a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
Anaplastic cytology is present in this hepatocellular carcinoma in a transgenic mouse.
Dual Transgenic Mouse Liver
  
Cholangiocarcinoma next to a more adenomatous lesion with hepatocyte cytological features in a 4-week-old transgenic mouse.
Dual Transgenic Mouse Liver
  
TGF alpha Transgenic Mouse Liver Lesions - Click on thumbnails to view larger images

(Images from Chapter 21 of Pathology of Genetically Engineered Mice (2000). JM Ward, JF Mahler, RR Maronpot, JP Sundberg, Eds. with permission of Iowa State University Press, Ames, Iowa)

Hepatocytomegaly and karyomegaly with apoptotic bodies (arrows).

TGF alpha Transgenic Mouse Liver
  
In situ hybridization demonstrating expression of TGF alpha. Seen with a normal lobular pattern of distribution in liver on left and with a more intense and irregular pattern of distribution in the carcinoma on the right.
TGF alpha Transgenic Mouse Liver
  
Glandular/acinar formation in a diethylnitrosamine-induced hepatocellular adenoma.
TGF alpha Transgenic Mouse Liver
  
 
Alb-uPA Transgenic Mice - Click on thumbnails to view larger images

Transgenic mice carrying an albumin promoter linked to mouse urokinase type plasminogen (uPA) activator have functionally compromised hepatocytes. High levels of hepatic production of uPA lead to hemorrhage and death of many of the mice shortly after birth. However, some mice survive due to chromosomal rearrangement of proliferating hepatocytes resulting in loss of significant functional components of the transgene. In these mice, the liver parenchyma is replaced by the transgene deficient hepatocytes within about 8 weeks. This replacement occurs by nodular regeneration of the transgene deficient hepatocytes. In some Alb-uPA mice there is complete loss of the transgene, and these mice eventually develop hepatocellular adenomas and carcinomas.
 

A large and a small nodule of regenerating hepatocytes in an Alb-uPA transgenic mouse.

Alb-uPA Transgenic Mouse Liver Lesions
  
Multiple large and small nodules of regenerating hepatocytes in an Alb-uPA transgenic mouse.
Alb-uPA Transgenic Mouse Liver Lesions
Alb-uPA Transgenic Mouse Liver Lesions
Alb-uPA Transgenic Mouse Liver Lesions
An aged uPA transgenic mouse with an hepatocellular adenoma. There is evidence of toxic hepatopathy in the adjacent hepatic parenchyma.
Alb-uPA Transgenic Mouse Liver Lesions
  
 

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