Phenotypes associated with this allele

• Allele Symbol: Tg(H2-D-Il15)3304Clgr
• Allele Name: transgene insertion 3304, Michael A Caligiuri
• Allele ID: MGI:3623278
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(H2-D-Il15)3304Clgr/?	FVB/N-Tg(H2-D-Il15)3304Clgr	MGI:3623280

Genotype
MGI:3623280

tg1

• Allelic Composition: Tg(H2-D-Il15)3304Clgr/?
• Genetic Background: FVB/N-Tg(H2-D-Il15)3304Clgr

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

Progressive alopecia in Tg(H2-D-Il15)3304Clgr/? mice

mortality/aging

premature death ( J:67478 )

• between 12 and 30 weeks of age, 70% of transgenic mice exhibit signs of illness - decreased activity, weight loss and breathing difficulty - and within a week become acutely moribund and die or must be euthanized

immune system

enlarged spleen ( J:67478 )

• moribund mice have massive splenomegaly

increased lymphocyte cell number ( J:67478 )

• by 6 weeks of age, all transgenic mice exhibit peripheral blood lymphocytosis, with lymphocyte counts averaging 31, 694 +/- 3, 267 /ul of blood versus 7, 983 +/- 503/ ul of control blood

• between 12 and 30 weeks of age, 70% of transgenic mice demonstrate progression of earlier lymphocytosis, with lymphocyte counts averaging 186,000 +/- 32,433/ul (range 46,000 - 606,000/ul) of blood

• peripheral blood smears from ill mice contain large numbers of lymphocytes, some with blast-like features and prominent nucleoli

increased NK cell number ( J:67478 )

• early lymphocytosis in transgenic mice is due to expansion primarily of functional - in terms of target cell lysis and induced interferon gamma secretion - DX5⁺CD3^-Ly49⁺ natural killer (NK) cells

abnormal T cell morphology ( J:67478 )

• the early, benign expansion of CD8⁺CD44^hiLy6c⁺ T cells observed in all transgenic mice is of polyclonal origin

• whereas absolute numbers of peripheral CD4⁺ T cells are comparable in 6 week old transgenic and control littermates, the number of CD8⁺ T cells is 10-fold greater in transgenic than in control mice

• flow cytometric analysis of lymphocytes from 22 affected (moribund) mice revealed the expanded population consistently bears the (somewhat heterogeneous) marker signature: CD3⁺TCR-beta⁺CD2⁺CD5⁺CD44⁺CD8^+/-DX5^mixed, although DX5⁺CD3^- NK cells remain elevated

abnormal T cell subpopulation ratio ( J:67478 )

• because of the expansion of the CD8⁺ T cell compartment, the ratio of CD4⁺ to CD8⁺ T cells is dramatically skewed toward the CD8⁺ population in transgenic mice (0.59 +/- 0.04 versus 3.26 +/- 0.1 in controls)

increased memory T cell number ( J:67478 )

• early lymphocytosis of transgenic mice is characterized by a secondary expanded subpopulation bearing the marker signature of memory T cells: CD44^hi CD62L^loCD69^-Ly6c^hi

increased spleen white pulp amount ( J:67478 )

• mice with highly elevated lymphocyte counts have expansion of the splenic white pulp

abnormal lymphocyte physiology ( J:67478 )

• transgenic mice that do not exhibit late clonal lymphocyte expansion nonetheless develop multiorgan lymphocytic infiltration

• mice with highly elevated lymphocyte counts have lymphocyte infiltration of the peritoneum and intraabdominal organs

enlarged lymph nodes ( J:67478 )

• mice with highly elevated lymphocyte counts have lymphadenopathy with disruption of the normal nodal architecture

abnormal inflammatory response ( J:67478 )

• large numbers of both CD3⁺ T lymphocytes and NK cells invade the spleens of ill mice

dermatitis ( J:67478 )

• mice with highly elevated lymphocyte counts exhibit skin inflammation characterized by heavy infiltration of the skin, primarily the dermis, by CD3⁺ lymphocytes and by mast cell infiltration

hematopoietic system

enlarged spleen ( J:67478 )

• moribund mice have massive splenomegaly

increased bone marrow cell number ( J:67478 )

• large numbers of both CD3⁺ T lymphocytes and NK cells invade the bone marrow of ill mice

increased lymphocyte cell number ( J:67478 )

• by 6 weeks of age, all transgenic mice exhibit peripheral blood lymphocytosis, with lymphocyte counts averaging 31, 694 +/- 3, 267 /ul of blood versus 7, 983 +/- 503/ ul of control blood

• between 12 and 30 weeks of age, 70% of transgenic mice demonstrate progression of earlier lymphocytosis, with lymphocyte counts averaging 186,000 +/- 32,433/ul (range 46,000 - 606,000/ul) of blood

• peripheral blood smears from ill mice contain large numbers of lymphocytes, some with blast-like features and prominent nucleoli

increased NK cell number ( J:67478 )

• early lymphocytosis in transgenic mice is due to expansion primarily of functional - in terms of target cell lysis and induced interferon gamma secretion - DX5⁺CD3^-Ly49⁺ natural killer (NK) cells

abnormal T cell morphology ( J:67478 )

• the early, benign expansion of CD8⁺CD44^hiLy6c⁺ T cells observed in all transgenic mice is of polyclonal origin

• whereas absolute numbers of peripheral CD4⁺ T cells are comparable in 6 week old transgenic and control littermates, the number of CD8⁺ T cells is 10-fold greater in transgenic than in control mice

• flow cytometric analysis of lymphocytes from 22 affected (moribund) mice revealed the expanded population consistently bears the (somewhat heterogeneous) marker signature: CD3⁺TCR-beta⁺CD2⁺CD5⁺CD44⁺CD8^+/-DX5^mixed, although DX5⁺CD3^- NK cells remain elevated

abnormal T cell subpopulation ratio ( J:67478 )

• because of the expansion of the CD8⁺ T cell compartment, the ratio of CD4⁺ to CD8⁺ T cells is dramatically skewed toward the CD8⁺ population in transgenic mice (0.59 +/- 0.04 versus 3.26 +/- 0.1 in controls)

increased memory T cell number ( J:67478 )

• early lymphocytosis of transgenic mice is characterized by a secondary expanded subpopulation bearing the marker signature of memory T cells: CD44^hi CD62L^loCD69^-Ly6c^hi

increased spleen white pulp amount ( J:67478 )

• mice with highly elevated lymphocyte counts have expansion of the splenic white pulp

abnormal lymphocyte physiology ( J:67478 )

• transgenic mice that do not exhibit late clonal lymphocyte expansion nonetheless develop multiorgan lymphocytic infiltration

• mice with highly elevated lymphocyte counts have lymphocyte infiltration of the peritoneum and intraabdominal organs

neoplasm

increased leukemia incidence ( J:67478 , J:97873 )

• molecular analysis of Tcrb gene rearrangements defined the late expanded lymphocyte populations of 48% (9/19) of ill transgenic mice as clonal, indicative of T-cell leukemia (J:67478)

• flow cytometric analysis of lymphocytes from 2 affected (moribund) mice revealed an expanded population of CD3^-TCR-beta^-CD8^-CD4^-DX5⁺ cells proposed to represent NK cell leukemias (J:67478)

• ~30% of transgenic mice develop clonal expansion of NK/T lymphocytes in multiple tissues that progresses to acute lymphoblastic leukemia (NK/T ALL) (J:97873)

liver/biliary system

abnormal liver morphology ( J:67478 )

• mice with highly elevated lymphocyte counts have liver involvement characterized by perivascular and sinusoidal lymphocyte infiltration

enlarged liver ( J:67478 )

• moribund mice have massive hepatomegaly

respiratory system

abnormal lung morphology ( J:67478 )

• mice with highly elevated lymphocyte counts have lung involvement ranging from heavy but confined infiltration around blood vessels to generalized infiltration involving the alveolar walls

integument

dermatitis ( J:67478 )

• mice with highly elevated lymphocyte counts exhibit skin inflammation characterized by heavy infiltration of the skin, primarily the dermis, by CD3⁺ lymphocytes and by mast cell infiltration

alopecia ( J:67478 )

• all mice with this transgene develop progressive alopecia beginning at 4-6 weeks of age, affecting initially the head and forelimbs and eventually 50-90% of the skin surface

hair follicle degeneration ( J:67478 )

hyperkeratosis ( J:67478 )

epidermal hyperplasia ( J:67478 )

spontaneous skin ulceration ( J:67478 )

growth/size/body

enlarged liver ( J:67478 )

• moribund mice have massive hepatomegaly

enlarged spleen ( J:67478 )

• moribund mice have massive splenomegaly