Phenotypes Associated with This Genotype

Genotype
MGI:5763310

• Allelic Composition: Tg(Fabp4-Phb*Y114F)#Smis/0
• Genetic Background: Not Specified

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

growth/size/body

obese ( J:227976 )

• mice start to gain weight around 1 month of age and become obese by 2-3 months of age, independent of diet

• ovariectomy in females blocks obesity development

enlarged spleen ( J:227976 )

♂ • tumor-bearing males develop splenomegaly

hematopoietic system

increased lymphocyte cell number ( J:227976 )

♂ • increase in lymphocyte population in tumors

abnormal spleen morphology ( J:227976 )

♂ • spleen of tumor-bearing males contains larger follicles, expanded cortical area, and increase in population of Reed-Steinberg cells (lacunar histiocytes)

enlarged spleen ( J:227976 )

♂ • tumor-bearing males develop splenomegaly

homeostasis/metabolism

decreased circulating ghrelin level ( J:227976 )

♂ • serum ghrelin level is decreased in both fasted and fed males

increased circulating ghrelin level ( J:227976 )

♀ • serum ghrelin level is increased in fasted females

increased circulating insulin-like growth factor I level ( J:227976 )

♂ • serum IGF-1 levels are increased in tumor-bearing mice

increased circulating leptin level ( J:227976 )

♂ • leptin levels are higher in males than females

abnormal circulating cytokine level ( J:227976 )

• serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IL-15, IL-18, INF-gamma and TNF-alpha) are decreased in tumor bearing males and to a lesser extent in non-tumor bearing males compared to wild-type males

• serum cytokine levels of IL-10, IL-12, IL-15, IL-18, IFN-gamma, and TNF-alpha in females are higher than in wild-type females

abnormal circulating chemokine level ( J:227976 )

♂ • serum chemokine levels of stromal cell-derived factor 1 and granulocyte chemotactic protein 2 are decreased in females but increased in males (of both non-tumor and tumor-bearing males)

♂ • serum C-C chemokine ligand 21 level is increased in males and further increased in tumor-bearing males

abnormal glucose homeostasis ( J:227976 )

♀ • ovariectomy in females results in impaired glucose homeostasis

increased circulating insulin level ( J:227976 )

♂ • serum insulin levels are higher in both fasted and fed males

impaired glucose tolerance ( J:227976 )

♂ • males exhibit impaired glucose tolerance at 6 months of age

insulin resistance ( J:227976 )

• males, but not females, exhibit impaired insulin tolerance at 6 months of age

• ovariectomy in females results in reduced insulin sensitivity

increased adiponectin level ( J:227976 )

♀ • adiponectin levels are increased in females

immune system

increased lymphocyte cell number ( J:227976 )

♂ • increase in lymphocyte population in tumors

abnormal spleen morphology ( J:227976 )

♂ • spleen of tumor-bearing males contains larger follicles, expanded cortical area, and increase in population of Reed-Steinberg cells (lacunar histiocytes)

enlarged spleen ( J:227976 )

♂ • tumor-bearing males develop splenomegaly

abnormal circulating cytokine level ( J:227976 )

• serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IL-15, IL-18, INF-gamma and TNF-alpha) are decreased in tumor bearing males and to a lesser extent in non-tumor bearing males compared to wild-type males

• serum cytokine levels of IL-10, IL-12, IL-15, IL-18, IFN-gamma, and TNF-alpha in females are higher than in wild-type females

abnormal circulating chemokine level ( J:227976 )

♂ • serum chemokine levels of stromal cell-derived factor 1 and granulocyte chemotactic protein 2 are decreased in females but increased in males (of both non-tumor and tumor-bearing males)

♂ • serum C-C chemokine ligand 21 level is increased in males and further increased in tumor-bearing males

abnormal lymph node morphology ( J:227976 )

♂ • males develop sinus histiocytosis with lymphadenopathy

♂ • tumor-bearing mice develop heterogenous histiocytosis containing histiocytic and dendritic cells

♂ • histiocytosis develops only in hyperinsulinemic males

enlarged lymph nodes ( J:227976 )

♂ • lymphadenopathy in males that develop sinus histiocytosis

neoplasm

increased tumor incidence ( J:227976 )

• males start to develop multiple tumors around 9 months of age with a prevalence of about 50%

• tumors develop unilaterally or bilaterally in the axillary and/or inguinal lymph nodes near the fore limbs and hind limbs, respectively

• tumors are characteristic of sinus histiocytosis with lymphadenopathy and show gradual expansion of eosinophilic histiocytes within lymph nodes during tumor growth

• females do not develop tumors, however ovariectomy in females results in the development of tumors in 50% of mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:227976