Phenotypes Associated with This Genotype

Genotype
MGI:6287975

• Allelic Composition: Atg5^tm1Myok/Atg5^tm1Myok; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv

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

growth/size/body

decreased body weight ( J:235399 )

• mice appear normal at weaning but fail to gain weight

hematopoietic system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

homeostasis/metabolism

increased circulating creatinine level ( J:235399 )

increased blood urea nitrogen level ( J:235399 )

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased urine protein level ( J:235399 )

immune system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased susceptibility to systemic lupus erythematosus ( J:235399 )

• mice develop a systemic lupus erythematosus-like disease (SLE)

increased autoantibody level ( J:235399 )

• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE

increased anti-nuclear antigen antibody level ( J:235399 )

increased anti-double stranded DNA antibody level ( J:235399 )

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

renal/urinary system

increased urine protein level ( J:235399 )

abnormal kidney morphology ( J:235399 )

• mice show indications of kidney damage and show increased functional markers of kidney injury

abnormal renal glomerulus morphology ( J:235399 )

• IgG and complement C1q deposition in the glomeruli of kidneys

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

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:235399