Phenotypes associated with this allele

• Allele Symbol: Inpp5d^tm1.1Wgk
• Allele Name: targeted mutation 1.1, William G Kerr
• Allele ID: MGI:3525663
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Inpp5d^tm1.1Wgk/Inpp5d^tm1.1Wgk	involves: 129S6/SvEvTac * C57BL/6J	MGI:3526523
cn2	Inpp5d^tm1Wgk/Inpp5d^tm1.1Wgk Tg(Mx1-cre)1Cgn/0	B6.Cg-Inpp5d^tm1Wgk/Inpp5d^tm1.1Wgk Tg(Mx1-cre)1Cgn	MGI:3830385

Genotype
MGI:3526523

hm1

• Allelic Composition: Inpp5d^tm1.1Wgk/Inpp5d^tm1.1Wgk
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

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

hematopoietic system

abnormal mononuclear cell differentiation ( J:94861 )

• increased numbers of Mac-1⁺Gr-1⁺ myeloid suppressor cells (20-fold increase) and other myelogranulocytic cell types (Mac-1⁺Gr-1^- and Gr-1⁺Mac-1^- subsets) in the spleen and lymph node

increased dendritic cell number ( J:94861 )

• the numbers of CD11c⁺Mac-1⁺ dendritic cells were significantly increased in the peripheral lymph node but not the spleen

increased monocyte cell number ( J:94861 )

• the numbers of CD11c^-Mac-1⁺ monocytes was increased in the spleen and lymph node

abnormal NK cell morphology ( J:95215 )

• adult homozygotes have an abnormal population of NK cells that expresses 10-fold higher surface levels of the NK receptor, Klrb1c (NK1.1) and have altered expression of MHC receptors

• NK cells survive longer than in wild-type

increased NK cell number ( J:95215 )

• two- to three-fold increase in peripheral NK cells in homozygous adult mice relative to wild-type

abnormal leukocyte physiology ( J:94861 )

• irradiated splenocytes and lymph node cells failed to stimulate allogeneic T cell proliferation and production of IL-2 in BALB/c splenocytes and lymph node cells indicating that homozygous null cells fail to present and prime an allogeneic T cell reasponse

• splenocytes do not process and present MHC class II-restricted T cell epitopes

• homozygous null myeloid suppressor cells suppress the ability of dendritic cells to prime allogeneic T cell responses

immune system

abnormal mononuclear cell differentiation ( J:94861 )

• increased numbers of Mac-1⁺Gr-1⁺ myeloid suppressor cells (20-fold increase) and other myelogranulocytic cell types (Mac-1⁺Gr-1^- and Gr-1⁺Mac-1^- subsets) in the spleen and lymph node

increased dendritic cell number ( J:94861 )

• the numbers of CD11c⁺Mac-1⁺ dendritic cells were significantly increased in the peripheral lymph node but not the spleen

increased monocyte cell number ( J:94861 )

• the numbers of CD11c^-Mac-1⁺ monocytes was increased in the spleen and lymph node

abnormal NK cell morphology ( J:95215 )

• adult homozygotes have an abnormal population of NK cells that expresses 10-fold higher surface levels of the NK receptor, Klrb1c (NK1.1) and have altered expression of MHC receptors

• NK cells survive longer than in wild-type

increased NK cell number ( J:95215 )

• two- to three-fold increase in peripheral NK cells in homozygous adult mice relative to wild-type

abnormal leukocyte physiology ( J:94861 )

• irradiated splenocytes and lymph node cells failed to stimulate allogeneic T cell proliferation and production of IL-2 in BALB/c splenocytes and lymph node cells indicating that homozygous null cells fail to present and prime an allogeneic T cell reasponse

• splenocytes do not process and present MHC class II-restricted T cell epitopes

• homozygous null myeloid suppressor cells suppress the ability of dendritic cells to prime allogeneic T cell responses

decreased susceptibility to graft versus host disease ( J:94861 , J:95215 )

• homozygotes did not reject allogeneic bone marrow transplants and had a normal life span and did not develop acute or chronic GVHD (J:94861)

• homozygotes failed to reject fully mismatched allogeneic marrow grafts and survived the bone marrow transplant without developing graft vs host disease (GVHD) compared to less than half of wild-type surviving (J:95215)

cellular

abnormal mononuclear cell differentiation ( J:94861 )

• increased numbers of Mac-1⁺Gr-1⁺ myeloid suppressor cells (20-fold increase) and other myelogranulocytic cell types (Mac-1⁺Gr-1^- and Gr-1⁺Mac-1^- subsets) in the spleen and lymph node

Genotype
MGI:3830385

cn2

• Allelic Composition: Inpp5d^tm1Wgk/Inpp5d^tm1.1Wgk; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Inpp5d^tm1Wgk/Inpp5d^tm1.1Wgk Tg(Mx1-cre)1Cgn

immune system

abnormal myeloid leukocyte morphology ( J:144110 )

• Cd11b⁺Gr⁺ myeloid suppressor cell (MySC) numbers are significantly increased in both the spleen and mesenteric lymph nodes after cre induction

• expansion is 5- to 10-fold higher than controls in the spleen and 10- to 20- fold higher in the lymph nodes after cre induction

• when cre expression is only partially induced, significant increase in MySC numbers are still observed

abnormal leukocyte physiology ( J:144110 )

• Cd11b ⁺Gr⁺ myeloid suppressor cell (MySC) have an enhanced ability on a per cell basis to suppress allogenic T cells in a mixed lymphocyte reaction

• priming of allogenic T cells by mutant splenocytes is also poor, an effect attributable to the enhanced MySC activity

hematopoietic system

abnormal myeloid leukocyte morphology ( J:144110 )

• Cd11b⁺Gr⁺ myeloid suppressor cell (MySC) numbers are significantly increased in both the spleen and mesenteric lymph nodes after cre induction

• expansion is 5- to 10-fold higher than controls in the spleen and 10- to 20- fold higher in the lymph nodes after cre induction

• when cre expression is only partially induced, significant increase in MySC numbers are still observed

abnormal leukocyte physiology ( J:144110 )

• Cd11b ⁺Gr⁺ myeloid suppressor cell (MySC) have an enhanced ability on a per cell basis to suppress allogenic T cells in a mixed lymphocyte reaction

• priming of allogenic T cells by mutant splenocytes is also poor, an effect attributable to the enhanced MySC activity