Phenotypes Associated with This Genotype

Genotype
MGI:6712638

• Allelic Composition: Riok2^{tm1c(KOMP)Wtsi}/Riok2⁺; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: involves: C57BL/6N * C57BL/10 * CBA/Ca

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

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:305794 )

• 8-12 week of mice exposed to acute hemolytic stress induced by phenylhydrazine treatment succumb faster to a lethal dose of phenylhydrazine than controls

hematopoietic system

abnormal erythropoiesis ( J:305794 )

• mice exhibit impaired erythropoiesis in the bone marrow

anemia ( J:305794 )

• mice over 60 weeks of age exhibit anemia

• 8-12 week of mice exposed to acute hemolytic stress (induced by nonlethal phenylhydrazine treatment) develop more severe anemia and have a delayed red blood cell recovery response compared to controls and succumb faster to a lethal dose of phenylhydrazine

• wild-type mice transplanted with mutant whole bone marrow develop anemia

• treatment of mice with a neutralizing IL-22 antibody reverses phenylhydrazine-induced anemia

increased granulocyte monocyte progenitor cell number ( J:305794 )

• the percentage of proliferating granulocyte-macrophage progenitors in the bone marrow is increased

decreased erythroid progenitor cell number ( J:305794 )

• anemia in young phenylhydrazine-administered mice seen on day 7 is preceded by a reduction in bone marrow RIII and RIV erythroid precursor frequency on day 6, indicating an erythroid differentiation defect

decreased erythrocyte cell number ( J:305794 )

• aged mice exhibit reduced peripheral blood red blood cell numbers

decreased hematocrit ( J:305794 )

• in aged mice

decreased hemoglobin content ( J:305794 )

• in aged mice

decreased neutrophil cell number ( J:305794 )

• mice exhibit a decreased percentage of neutrophils (neutropenia)

increased NK T cell number ( J:305794 )

• aged mice show increased numbers of natural killer T cells

increased monocyte cell number ( J:305794 )

• mice exhibit an increased percentage of monocytes (monocytosis)

increased myeloid cell number ( J:305794 )

• LSK (lineage^-Sca-1⁺Kit⁺) cells from the bone marrow supplemented with growth factors give rise to an increased percentage of CD11b+ myeloid cells, indicating a cell-intrinsic myeloproliferative effect

increased hematopoietic stem cell number ( J:305794 )

• frequency and numbers of early hematopoietic progenitors are normal in young mice, however long-term hematopoietic stem cells (LT-HSCs) are increased in the bone marrow of aged mice

abnormal CD4-positive, alpha beta T cell morphology ( J:305794 )

• aged mice show increased numbers of splenic IL-22+CD4+T cells

abnormal hematopoietic system physiology ( J:305794 )

• mice exhibit an increase in apoptosis of erythroid precursors

• erythroid precursors show a decrease in cell quiescence with cell cycle block at the G1 phase

• treatment of mice with a neutralizing IL-22 antibody reduces the frequency of apoptotic erythroid precursors

abnormal CD4-positive, alpha-beta T cell physiology ( J:305794 )

• TH22 cells secrete elevated concentrations of IL-22

abnormal bone marrow cell physiology ( J:305794 )

• bone marrow cells show reduced nascent protein synthesis in vivo

homeostasis/metabolism

abnormal circulating interleukin level ( J:305794 )

• the concentration of IL-22 in the serum and bone marrow fluid of aged mice is higher than in controls

increased susceptibility to xenobiotic induced morbidity/mortality ( J:305794 )

• 8-12 week of mice exposed to acute hemolytic stress induced by phenylhydrazine treatment succumb faster to a lethal dose of phenylhydrazine than controls

increased physiological sensitivity to xenobiotic ( J:305794 )

• 8-12 week of mice exposed to acute hemolytic stress induced by nonlethal phenylhydrazine treatment develop more severe anemia and have a delayed red blood cell recovery response compared to controls

• treatment of mice with a neutralizing IL-22 antibody reverses phenylhydrazine-induced anemia

immune system

abnormal CD4-positive, alpha-beta T cell physiology ( J:305794 )

• TH22 cells secrete elevated concentrations of IL-22

abnormal circulating interleukin level ( J:305794 )

• the concentration of IL-22 in the serum and bone marrow fluid of aged mice is higher than in controls

abnormal immune system morphology ( J:305794 )

• aged mice show increased numbers of innate lymphoid cells

decreased neutrophil cell number ( J:305794 )

• mice exhibit a decreased percentage of neutrophils (neutropenia)

increased NK T cell number ( J:305794 )

• aged mice show increased numbers of natural killer T cells

increased monocyte cell number ( J:305794 )

• mice exhibit an increased percentage of monocytes (monocytosis)

abnormal CD4-positive, alpha beta T cell morphology ( J:305794 )

• aged mice show increased numbers of splenic IL-22+CD4+T cells

abnormal interleukin secretion ( J:305794 )

• naive T cells polarized toward the TH22 cell lineage show an increase in IL-22 secretion