Phenotypes Associated with This Genotype

Genotype
MGI:4939884

• Allelic Composition: Rxra^tm1Krc/Rxra^tm1Krc; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

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

renal/urinary system

increased renal glomerulus apoptosis ( J:168799 )

• increase in the number of apoptotic cells in the glomeruli

increased urine protein level ( J:168799 )

• mutants exhibit excretion of high molecular weight proteins in the urine

albuminuria ( J:168799 )

• mutants exhibit excretion of albumin in the urine

abnormal kidney morphology ( J:168799 )

• females develop severe nephropathy at 4-6 months of age

enlarged kidney ( J:168799 )

• kidney hypertrophy

increased kidney weight ( J:168799 )

• increase in kidney weight due to glomerulomegaly

abnormal nephron morphology ( J:168799 )

• nephrons exhibit coarsening and fusion of podocyte foot processes

abnormal podocyte foot process morphology ( J:168799 )

• cell destruction in the glomeruli is indicated by the accumulation of electrolucent material in podocyte foot processes

fused podocyte foot processes ( J:168799 )

• fusion of podocyte foot processes

increased renal glomerulus basement membrane thickness ( J:168799 )

• glomerular basement membrane thickening

abnormal renal glomerulus morphology ( J:168799 )

• increase in glomerular cell number

increased mesangial cell number ( J:168799 )

• mesangial hypercellularity

glomerulonephritis ( J:168799 )

• severe glomerular inflammation associated with increased renal macrophage infiltration

expanded mesangial matrix ( J:168799 )

• mesangial matrix expansion

renal glomerulus hypertrophy ( J:168799 )

• glomerulomegaly; glomeruli are enlarged in focal regions within the kidneys

homeostasis/metabolism

increased circulating creatine level ( J:168799 )

increased urine protein level ( J:168799 )

• mutants exhibit excretion of high molecular weight proteins in the urine

albuminuria ( J:168799 )

• mutants exhibit excretion of albumin in the urine

immune system

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

abnormal peritoneal macrophage morphology ( J:168799 )

• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages

increased IgG level ( J:168799 )

• mutants exhibit a marked deposition of IgG in the mesangial matrix

increased IgM level ( J:168799 )

• mutants exhibit a marked deposition of IgM in the mesangial matrix

abnormal macrophage activation involved in immune response ( J:168799 )

• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli

increased autoantibody level ( J:168799 )

• mutants develop autoantibodies against nuclear proteins, ssDNA, and dsDNA

increased anti-nuclear antigen antibody level ( J:168799 )

increased anti-double stranded DNA antibody level ( J:168799 )

increased anti-single stranded DNA antibody level ( J:168799 )

glomerulonephritis ( J:168799 )

• severe glomerular inflammation associated with increased renal macrophage infiltration

hematopoietic system

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

abnormal peritoneal macrophage morphology ( J:168799 )

• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages

increased IgG level ( J:168799 )

• mutants exhibit a marked deposition of IgG in the mesangial matrix

increased IgM level ( J:168799 )

• mutants exhibit a marked deposition of IgM in the mesangial matrix

abnormal macrophage activation involved in immune response ( J:168799 )

• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli

cellular

increased mesangial cell number ( J:168799 )

• mesangial hypercellularity

increased renal glomerulus apoptosis ( J:168799 )

• increase in the number of apoptotic cells in the glomeruli

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

growth/size/body

enlarged kidney ( J:168799 )

• kidney hypertrophy

increased kidney weight ( J:168799 )

• increase in kidney weight due to glomerulomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:168799