Phenotypes associated with this allele

• Allele Symbol: Ncstn^tm1.1Akli
• Allele Name: targeted mutation 1.1, Apostolos Klinakis
• Allele ID: MGI:5009035
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(VAV1-cre)1Graf/0	involves: 129	MGI:5496430
cn2	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(Upk2-cre,-EGFP)#Akli/0	involves: 129	MGI:5779426
cn3	Gt(ROSA)26Sor^tm1.1(rtTA2S*M2)Whsu/Gt(ROSA)26Sor^+ Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(tetO-cre)1Jaw/0	involves: 129 * 129S6/SvEvTac * C57BL/6	MGI:5779422
cn4	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(Mx1-cre)1Cgn/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:5009036
cn5	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(VAV1-cre)1Graf/0	involves: 129 * C57BL/6 * SJL	MGI:5009037
cn6	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5496428

Genotype
MGI:5496430

cn1

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129

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

mortality/aging

premature death ( J:196407 )

immune system

enlarged spleen ( J:196407 )

abnormal splenocyte physiology ( J:196407 )

• splenocytes transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood compared with cells from control mice

• however, transplanted cells do not induce lethal myeloid leukemia

hematopoietic system

enlarged spleen ( J:196407 )

abnormal splenocyte physiology ( J:196407 )

• splenocytes transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood compared with cells from control mice

• however, transplanted cells do not induce lethal myeloid leukemia

growth/size/body

enlarged spleen ( J:196407 )

Genotype
MGI:5779426

cn2

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(Upk2-cre,-EGFP)#Akli/0
• Genetic Background: involves: 129

neoplasm

increased urinary bladder carcinoma incidence ( J:227748 )

• within 2-6 months of age, mice develop bladder tumors that consist of simple and nodular hyperplasia, as well as high-grade dysplasia and carcinoma in situ showing basal characteristics

renal/urinary system

increased urinary bladder carcinoma incidence ( J:227748 )

• within 2-6 months of age, mice develop bladder tumors that consist of simple and nodular hyperplasia, as well as high-grade dysplasia and carcinoma in situ showing basal characteristics

hydronephrosis ( J:227748 )

• mice develop occasional unilateral hydronephrosis within 2-6 months due to ureter obstruction

ureter obstruction ( J:227748 )

• due to bladder tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:227748

Genotype
MGI:5779422

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(rtTA2S*M2)Whsu}/Gt(ROSA)26Sor⁺; Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6

neoplasm

increased urinary bladder carcinoma incidence ( J:227748 )

• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer

• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation

• tumors invade the lamina and muscularis propria

• marker analysis indicates that tumors are related to human basal BLCA3 subtype

renal/urinary system

increased urinary bladder carcinoma incidence ( J:227748 )

• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer

• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation

• tumors invade the lamina and muscularis propria

• marker analysis indicates that tumors are related to human basal BLCA3 subtype

hydronephrosis ( J:227748 )

• 12 of 18 mice develop unilateral or bilateral hydronephrosis as early as 2 weeks after dox treatment due to obstruction of the upper ureter by tumor masses

ureter obstruction ( J:227748 )

• due to bladder tumors in dox treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:227748

Genotype
MGI:5009036

cn4

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

mortality/aging

premature death ( J:172442 )

• do not survive more than 20 weeks after induction of cre mediated recombination

hematopoietic system

abnormal definitive hematopoiesis ( J:172442 )

• significant reduction of the lymphoid-biased multipotential progenitor population (L-MPP) after induction of cre mediated recombination

• striking increase in the absolute numbers of both bone marrow and spleen granulocyte/monocyte progenitors cells after induction of cre mediated recombination

• decrease of the megakaryocyte?erythrocyte progenitor population after induction of cre mediated recombination

• progenitor cells display an increase in their self-renewal capacity after induction of cre mediated recombination

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis after induction of cre mediated recombination

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis after induction of cre mediated recombination

• increase in monocyte numbers in the bone marrow and liver after induction of cre mediated recombination

abnormal hematopoietic stem cell morphology ( J:172442 )

• de-repression of an extended myeloid-specific program in LSK cells

increased hematopoietic stem cell number ( J:172442 )

• increase in LSK numbers after induction of cre mediated recombination

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells after induction of cre mediated recombination

enlarged spleen ( J:172442 )

• after induction of cre mediated recombination

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp after induction of cre mediated recombination

neoplasm

increased leukemia incidence ( J:172442 )

• similarity to chronic myelomonocytic leukemia after induction of cre mediated recombination

immune system

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis after induction of cre mediated recombination

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis after induction of cre mediated recombination

• increase in monocyte numbers in the bone marrow and liver after induction of cre mediated recombination

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells after induction of cre mediated recombination

enlarged spleen ( J:172442 )

• after induction of cre mediated recombination

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp after induction of cre mediated recombination

growth/size/body

enlarged spleen ( J:172442 )

• after induction of cre mediated recombination

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:172442

Genotype
MGI:5009037

cn5

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

premature death ( J:172442 )

• do not survive more than 20 weeks

hematopoietic system

abnormal definitive hematopoiesis ( J:172442 )

• significant reduction of the lymphoid-biased multipotential progenitor population (L-MPP)

• striking increase in the absolute numbers of both bone marrow and spleen granulocyte/monocyte progenitors cells

• decrease of the megakaryocyte?erythrocyte progenitor population

• progenitor cells display an increase in their self-renewal capacity

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis

• increase in monocyte numbers in the bone marrow and liver

abnormal hematopoietic stem cell morphology ( J:172442 )

• de-repression of an extended myeloid-specific program in LSK cells

increased hematopoietic stem cell number ( J:172442 )

• increase in LSK numbers

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells

enlarged spleen ( J:172442 )

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp

neoplasm

increased leukemia incidence ( J:172442 )

• similarity to chronic myelomonocytic leukemia

immune system

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis

• increase in monocyte numbers in the bone marrow and liver

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells

enlarged spleen ( J:172442 )

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp

growth/size/body

enlarged spleen ( J:172442 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:172442

Genotype
MGI:5496428

cn6

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

mortality/aging

premature death ( J:196407 )

• mice die at 26 weeks

immune system

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells

myeloid hyperplasia ( J:196407 )

• increased circulating blast-like cells at 7 weeks after birth

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

increased leukocyte cell number ( J:196407 )

• with an increase in absolute myelomonocytic and blast-like cells 7 weeks after birth

neoplasm

abnormal tumor pathology ( J:196407 )

• spleen tumor cells transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood and lethality compared with cells from control mice

increased leukemia incidence ( J:196407 )

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

hematopoietic system

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells

abnormal common myeloid progenitor cell morphology ( J:196407 )

• enlarged granulocyte-macrophage progenitor (GMP) compartment

myeloid hyperplasia ( J:196407 )

• increased circulating blast-like cells at 7 weeks after birth

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

increased leukocyte cell number ( J:196407 )

• with an increase in absolute myelomonocytic and blast-like cells 7 weeks after birth

growth/size/body

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells