Mouse Genome Informatics
cx1
    Prkcqtm1Litt/Prkcqtm1Litt
Tg(Lck-Notch3)#Issc/0

involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• compared with Tg(lck-Notch3)#Issc mice
• 35% of mice die prior to 20 weeks of age
• of mice that survive beyond 20 weeks, 50% die over 30 weeks of age and 20% survive at 50 weeks of age

tumorigenesis
• 40% of mice that survive beyond 20 weeks of age exhibit lymphoproliferative disease (enlarged upper mediastium and 2- to 3-fold increase in spleen size and weight) compared with 95% of Tg(lck-Notch3)#Issc mice

immune system
• 2- to 3-fold in 40% of mice that survive beyond 20 weeks of age
• 2- to 3-fold in 40% of mice that survive beyond 20 weeks of age

growth/size/body
• 40% of mice that survive beyond 20 weeks of age exhibit enlarged upper mediastium compared with wild-type mice

hematopoietic system
• 2- to 3-fold in 40% of mice that survive beyond 20 weeks of age
• 2- to 3-fold in 40% of mice that survive beyond 20 weeks of age


Mouse Genome Informatics
tg2
    Tg(Lck-Notch3)#Issc/0
involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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)

tumorigenesis
• tumor cell infiltration is seen in the liver, lungs, kidney, bone marrow and peripheral blood, indicating leukemic phase of the disease
• 95% of mice die by 16 weeks of age with multicentric T-cell lymphomas
• 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

behavior/neurological

immune system
• hyperplastic thymus is seen in some mutants at 5-6 weeks of age
• in 3 week old mutants, particularly the late double negative cells
• 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
• 5- to 6-fold increase in size and weight of spleen at 5-6 weeks of age
• 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
• hyperplastic thymus is seen in some mutants at 5-6 weeks of age
• in 3 week old mutants, particularly the late double negative cells
• 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
• 5- to 6-fold increase in size and weight of spleen at 5-6 weeks of age

endocrine/exocrine glands
• hyperplastic thymus is seen in some mutants at 5-6 weeks of age
• in 3 week old mutants, particularly the late double negative cells

Mouse Models of Human Disease
OMIM IDRef(s)
Leukemia, Acute Lymphoblastic; ALL 613065 J:63300