Phenotypes Associated with This Genotype

Genotype
MGI:4843447

• Allelic Composition: Tg(Lck-Notch3)#Issc/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

mortality/aging

premature death ( J:63300 , J:96010 )

• 80% die between 10-12 weeks of age and by 16 weeks of age, 95% die (J:63300)

• 95% of mice die by 16 weeks of age with multicentric T-cell lymphomas (J:96010)

neoplasm

increased T cell derived lymphoma incidence ( J:96010 )

• 95% of mice die by 16 weeks of age with multicentric T-cell lymphomas

increased lymphoblastic lymphoma incidence ( J:63300 )

• thymus, spleen, and lymph nodes show massive infiltration by a monotonous lymphoblastic cell population

• mutants develop aggressive multicentric T-cell lymphomas showing features of lymphoblastic lymphoma with high penetrance by 7 weeks of age

• tumors sustain characteristics of immature thymocytes, including expression of CD25, pTalpha, and activated NF-kappaB

increased acute lymphoblastic leukemia incidence ( J:63300 )

• tumor cell infiltration is seen in the liver, lungs, kidney, bone marrow and peripheral blood, indicating leukemic phase of the disease

behavior/neurological

lethargy ( J:63300 )

hunched posture ( J:63300 )

immune system

thymus hyperplasia ( J:63300 )

• hyperplastic thymus is seen in some mutants at 5-6 weeks of age

increased thymocyte number ( J:63300 )

• in 3 week old mutants, particularly the late double negative cells

enlarged spleen ( J:63300 )

• 5- to 6-fold increase in size and weight of spleen at 5-6 weeks of age

abnormal T cell differentiation ( J:63300 )

• disruption of thymocyte differentiation; all thymocyte subsets express high levels of CD25 and are broadly distributed in the cortex and medulla of the thymus, indicating a failure to downregulate CD25 expression the occurs normally in double positive and single positive subsets after 17-18 dpc

increased double-negative T cell number ( J:63300 )

enlarged lymph nodes ( J:63300 )

• 5- to 6-fold increase in size and weight of peripheral (axillary, cervical, and abdominal) lymph nodes at 5-6 weeks of age

hematopoietic system

thymus hyperplasia ( J:63300 )

• hyperplastic thymus is seen in some mutants at 5-6 weeks of age

increased thymocyte number ( J:63300 )

• in 3 week old mutants, particularly the late double negative cells

enlarged spleen ( J:63300 )

• 5- to 6-fold increase in size and weight of spleen at 5-6 weeks of age

abnormal T cell differentiation ( J:63300 )

• disruption of thymocyte differentiation; all thymocyte subsets express high levels of CD25 and are broadly distributed in the cortex and medulla of the thymus, indicating a failure to downregulate CD25 expression the occurs normally in double positive and single positive subsets after 17-18 dpc

increased double-negative T cell number ( J:63300 )

endocrine/exocrine glands

thymus hyperplasia ( J:63300 )

• hyperplastic thymus is seen in some mutants at 5-6 weeks of age

increased thymocyte number ( J:63300 )

• in 3 week old mutants, particularly the late double negative cells

increased T cell derived lymphoma incidence ( J:96010 )

• 95% of mice die by 16 weeks of age with multicentric T-cell lymphomas

increased lymphoblastic lymphoma incidence ( J:63300 )

• thymus, spleen, and lymph nodes show massive infiltration by a monotonous lymphoblastic cell population

• mutants develop aggressive multicentric T-cell lymphomas showing features of lymphoblastic lymphoma with high penetrance by 7 weeks of age

• tumors sustain characteristics of immature thymocytes, including expression of CD25, pTalpha, and activated NF-kappaB

growth/size/body

enlarged spleen ( J:63300 )

• 5- to 6-fold increase in size and weight of spleen at 5-6 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute lymphoblastic leukemia		DOID:9952	OMIM:247640 OMIM:613065	J:63300