Phenotypes Associated with This Genotype

Genotype
MGI:2680724

• Allelic Composition: Osmr^tm1Mtan/Osmr^tm1Mtan
• Genetic Background: B6.129S-Osmr^tm1Mtan

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

hematopoietic system

hematopoietic system phenotype ( J:86261 )

N • homozygotes display normal kinetics of erythrocyte recovery after acute hemolysis induced by phenylhydrazine, as determined by measuring peripheral red cells, reticulocytes, and CFU-Es in bone marrow (BM) and spleen

N • in addition, homozygotes show normal kinetics of recovery of BM progenitors after 5-fluorouracil-induced myelosuppression

abnormal definitive hematopoiesis ( J:86261 )

• homozygotes exhibit impaired hematopoiesis in the bone marrow, and increased hematopoiesis in the spleen

abnormal common myeloid progenitor cell morphology ( J:86261 )

• in clonal culture assays, homozygotes show a significant reduction in the number of CFU-GEMMs, CFU-MEs, and BFU-Es in the bone marrow (BM) relative to wild-type mice

• in contrast to the BM, the number of CFU-GEMMs, CFU-MEs, and BFU-Es in mutant spleen is elevated relative to that observed in wild-type mice

• whereas no significant differences are observed in the number of granulocyte-macrophage colony-forming cells (GM-CFCs), including granulocyte CFUs (CFU-Gs), macrophage CFUs (CFU-Ms), and granulocyte-macrophage CFUs (CFU-GMs) in the mutant BM, the numbers of all types of GM-CFCs in mutant spleen are elevated relative to wild-type mice, indicating an opposite effect on hematopoiesis in BM and spleen

• in BM transplantation experiments, neonatal homozygotes engrafted with wild-type BM cells fail to produce erythrocytic and megakaryocytic progenitors to the levels observed in wild-type mice, indicating an effect on the hematopoietic microenvironment

• conversely, wild-type mice reconstituted with homozygous mutant BM cells exhibit a reduction in erythrocytic and megakaryocytic progenitors in the BM, whereas the GM-CFC number remains unchanged

• interestingly, hematopoietic progenitors in spleen are increased in homozygotes engrafted with either wild-type or homozygoys mutant BM cells, whereas they are not increased in wild-type mice that receive either wild-type or mutant BM cells

anemia ( J:86261 )

• homozygotes are slightly anemic relative to wild-type mice

decreased megakaryocyte cell number ( J:86261 )

• homozygotes show a significant reduction in the number of mature megakaryocytes in the BM relative to wild-type mice, as measured in H&E stained femoral sections

abnormal erythroid progenitor cell morphology ( J:86261 )

• in clonal culture assays, homozygotes show a significant reduction in the number of CFU-Es in the BM relative to wild-type mice

• in contrast to the BM, the number of CFU-Es in mutant spleen is significantly increased relative to that observed in wild-type mice

abnormal megakaryocyte progenitor cell morphology ( J:86261 )

• homozygotes show a significant reduction in the number of megakaryocyte progenitors, as determined in liquid cultures of BM cells

decreased erythrocyte cell number ( J:86261 )

• homozygotes show a significant reduction in the mean number of peripheral erythrocytes relative to wild-type mice (894 64 x 10⁴/mL vs 1028 52 x 10⁴/mL, respectively)

• in contrast, the mean number of peripheral white blood cells remains relatively unaffected

decreased hematocrit ( J:86261 )

• homozygotes display a reduced hematocrit relative to wild-type mice

thrombocytopenia ( J:86261 )

• homozygotes show a significant reduction in the mean number of peripheral platelets relative to wild-type mice (82 10 x 10⁴/mL vs 106 15 x 10⁴/mL, respectively)

adipose tissue

increased subcutaneous adipose tissue amount ( J:214124 )

• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type

increased epididymal fat pad weight ( J:214124 )

• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type

white adipose tissue inflammation ( J:214124 )

• mice fed a high-fat diet exhibit exacerbation of adipose tissue inflammation, with an increase in total number of F4/80-positive macrophages per weight of adipose tissue, with higher percentages of CD11c-positive M1-type and CD206-positive M2-type macrophages, lower percentage of CD11c/Cd2k06-double-negative cells among the total number of F4/80-positive macrophages and an increase in inflammatory markers

growth/size/body

increased susceptibility to diet-induced obesity ( J:214124 )

• mice fed a high-fat diet develop obesity; mutants gain more weight than wild-type at 4 weeks on the high-fat diet and remain heavier

• however, in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, mutants show similar body weight to wild-type mice

increased liver weight ( J:214124 )

• mice fed a high-fat diet exhibit increased liver weight

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:214124 )

• mice fed a high-fat diet develop obesity; mutants gain more weight than wild-type at 4 weeks on the high-fat diet and remain heavier

• however, in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, mutants show similar body weight to wild-type mice

increased circulating glucose level ( J:214124 )

• mice fed a high-fat diet begin to show an increase in blood glucose concentrations after 6 weeks on the diet

• mice fed a high-fat diet show increased blood glucose concentration under both fed and fasted states after 8 weeks of the diet

• in a pair-feeding study in which mutant mice receive the average amount of food consumed by wild-type mice, none of the metabolic phenotypes seen in mutants are affected by this decrease in food intake

increased circulating insulin level ( J:214124 )

• mice fed a high-fat diet begin to show an increase in serum insulin concentration after 1 week on the diet and this continues to increase for 8 weeks

increased circulating leptin level ( J:214124 )

• mice fed a high-fat diet show increased leptin serum concentration compared to wild-type

increased circulating cholesterol level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum total cholesterol concentrations in both fed and fasted states

increased circulating free fatty acids level ( J:214124 )

• mice fed a high-fat diet show a tendency for increased serum free fatty acids concentration in both fed and fasted states

increased circulating triglyceride level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum triglyceride concentrations in both fed and fasted states

increased circulating interleukin-10 level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum concentrations of IL-10

increased circulating tumor necrosis factor level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha

impaired glucose tolerance ( J:214124 )

• mice fed a high-fat diet show reduced glucose tolerance

decreased liver glycogen level ( J:214124 )

• mice fed a high-fat diet exhibit fewer glycogen granules in hepatocytes than wild-type mice

insulin resistance ( J:214124 )

• mice fed a high-fat diet develop insulin resistance

increased liver cholesterol level ( J:214124 )

• mice fed a high-fat diet show increased total cholesterol levels in the liver

increased liver triglyceride level ( J:214124 )

• mice fed a high-fat diet show increased triglyceride levels in the liver

integument

increased subcutaneous adipose tissue amount ( J:214124 )

• mice fed a high-fat diet show increased weights of epididymal and subcutaneous adipose tissues compared to wild-type

liver/biliary system

increased liver weight ( J:214124 )

• mice fed a high-fat diet exhibit increased liver weight

decreased liver glycogen level ( J:214124 )

• mice fed a high-fat diet exhibit fewer glycogen granules in hepatocytes than wild-type mice

increased liver cholesterol level ( J:214124 )

• mice fed a high-fat diet show increased total cholesterol levels in the liver

increased liver triglyceride level ( J:214124 )

• mice fed a high-fat diet show increased triglyceride levels in the liver

hepatic steatosis ( J:214124 )

• mice fed a high-fat diet exhibit severe hepatic steatosis

endocrine/exocrine glands

increased pancreatic beta cell number ( J:214124 )

• mice fed a high-fat diet exhibit hyperplasia of beta-cells in pancreas

immune system

increased circulating interleukin-10 level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum concentrations of IL-10

increased circulating tumor necrosis factor level ( J:214124 )

• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha

increased inflammatory response ( J:214124 )

• mice fed a high-fat diet exhibit increased serum concentrations of TNF-alpha, IL-10, and serum amyloid A, indicating elevation of systemic inflammation

white adipose tissue inflammation ( J:214124 )

• mice fed a high-fat diet exhibit exacerbation of adipose tissue inflammation, with an increase in total number of F4/80-positive macrophages per weight of adipose tissue, with higher percentages of CD11c-positive M1-type and CD206-positive M2-type macrophages, lower percentage of CD11c/Cd2k06-double-negative cells among the total number of F4/80-positive macrophages and an increase in inflammatory markers

behavior/neurological

increased food intake ( J:214124 )

• mice fed a high-fat diet show increased amount of food intake compared to wild-type mice