Phenotypes Associated with This Genotype

Genotype
MGI:5897270

• Allelic Composition: Lbr^ic-J/Lbr⁺
• Genetic Background: (NZW/LacJ x C57BL/6J-Lbr^ic-J/J)F1

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

hematopoietic system

enlarged spleen ( J:234168 )

♀ • females, but not males, show splenomegaly at 9 months of age

abnormal neutrophil morphology ( J:234168 )

• neutrophils of both males and females show alternations in nuclear morphology

immune system

enlarged spleen ( J:234168 )

♀ • females, but not males, show splenomegaly at 9 months of age

abnormal neutrophil morphology ( J:234168 )

• neutrophils of both males and females show alternations in nuclear morphology

increased susceptibility to systemic lupus erythematosus ( J:234168 )

♀ • females develop lupus autoimmunity, with induction of several autoantibodies, including anti-modified histones, IgG2 antibodies recognizing chromatin, and IgM directed against calreticulin, kidney damage and splenomegaly

increased autoantibody level ( J:234168 )

♀ • females show development of autoimmunity directed against components of the A-type lamina, but not lamin A/C itself

♀ • anti-neutrophil autoreactivity mediated by IgM is directed against calreticulin, but not myeloperoxidase or proteinase 3, with 9 of 11 females showing detectable anti-calreticulin IgM titers

increased anti-nuclear antigen antibody level ( J:234168 )

♀ • females exhibit an increase in serum anti-nuclear antibody levels

♀ • females develop an anti-nuclear autoimmune response that selectively recognizes specific modified histones

increased anti-chromatin antibody level ( J:234168 )

♀ • females exhibit an increase in serum titers of anti-chromatin antibodies

♀ • IgG2a, IgG2b, IgG2c, and IgM are prevalent anti-chromatin immunoglobulin subtypes in sera

♀ • however, distribution of anti-double stranded DNA does not differ from controls

renal/urinary system

abnormal kidney morphology ( J:234168 )

♀ • females, but not males, develop kidney damage, with formation of inflammatory foci

abnormal renal glomerulus morphology ( J:234168 )

♀ • females show glomerular deposition of immune complexes

glomerulosclerosis ( J:234168 )

♀ • females exhibit moderate-to-severe glomerulosclerosis and tubulointerstitial fibrosis with perivascular infiltration of mononuclear cells

renal interstitial fibrosis ( J:234168 )

♀ • females exhibit moderate-to-severe tubulointerstitial fibrosis

growth/size/body

enlarged spleen ( J:234168 )

♀ • females, but not males, show splenomegaly at 9 months of age

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:234168