Phenotypes Associated with This Genotype

Genotype
MGI:5009691

cn2

• Allelic Composition: Notch1^tm2Rko/Notch1^tm3(cre)Rko
• Genetic Background: involves: 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Corneal plaques and increased angiogenesis in the ear of Notch1^tm2Rko/Notch1^tm3(cre)Rko mice

growth/size/body

enlarged spleen ( J:171829 )

• reactive splenomegaly is observed at post mortem

mortality/aging

premature death ( J:171829 )

• life expectancy is significantly reduced in mutants (420 days) compared to wild-type (600 days)

neoplasm

increased hemangioma incidence ( J:171829 )

• 11/13 mice have hemangiosarcoma/vascular tumors, some of which involve multiple organs including the ovary, testis, skin, lymph node, uterus, and colon; liver is the primary site (82% of mice)

vision/eye

abnormal cornea morphology ( J:171829 )

• corneal hyperplasia develops by 2-3 months in all animals

cornea vascularization ( J:171829 )

• normal cornea is replaced by a vascularized epidermis-like structure

cornea deposits ( J:171829 )

• mice develop corneal plaques by 2-3 months; this increases in severity with age

hematopoietic system

extramedullary hematopoiesis ( J:171829 )

• observed in the spleen in granulocytic, erythrocytic, and megakaryocytic lineages with no bias in B/T cell lineages

abnormal spleen morphology ( J:171829 )

• marked expansion of the interfollicular compartments is observed

enlarged spleen ( J:171829 )

• reactive splenomegaly is observed at post mortem

liver/biliary system

chronic liver inflammation ( J:171829 )

• dense, chronic inflammatory infiltrates are observed around the bile ducts

abnormal liver morphology ( J:171829 )

• liver contains numerous reddened large blood filled spaces consistent with occurrence of vascular tumors

abnormal hepatic cord morphology ( J:171829 )

• hepatic cords are separated by inflammatory infiltrate

abnormal liver parenchyma morphology ( J:171829 )

• normal parenchyma is replaced either by solid, hypercellular tissue composed of spindle and epithelioid cells interspersed with many vascular channels or by irregular vascular channels lined by cells with scant-to-moderate eosinophilic cytoplasm and round-to-oval nuclei; nuclei of these cells of endothelial origin were hyperchromatic or contained coarse chromatin

abnormal liver lobule morphology ( J:171829 )

• liver lobes have irregular contours

dilated liver sinusoidal space ( J:171829 )

pale liver ( J:171829 )

• on post mortem liver is observed to be pale, with many irregular reddened foci; some patches are almost white

cardiovascular system

dilated liver sinusoidal space ( J:171829 )

increased angiogenesis ( J:171829 )

• increased angiogenesis is observed in the ear

hemoperitoneum ( J:171829 )

• observed in 6/7 naturally deceased mice

cornea vascularization ( J:171829 )

• normal cornea is replaced by a vascularized epidermis-like structure

immune system

abnormal spleen morphology ( J:171829 )

• marked expansion of the interfollicular compartments is observed

enlarged spleen ( J:171829 )

• reactive splenomegaly is observed at post mortem

chronic liver inflammation ( J:171829 )

• dense, chronic inflammatory infiltrates are observed around the bile ducts