• some homozygotes display symptoms of systemic lupus erythematosus at 6-8 months of age and die

• 17/49 homozygotes exhibit splenomegaly

• Background Sensitivity: on a mixed 129/B6 background, mice develop symptoms similar to systemic lupus erythematosus

• mice show anti-nuclear antibodies

• 56% of male mice and 73% of female mice display anti-nuclear antibodies compared to 15% of male and 35% of female wild-type mice

• 21/49 show perivascular leukocytic infiltration in the kidney

• in males, 19% show glomerulonephritis compared to 0% of wild-type; 31% of female heterozygotes show glomerulonephritis compared to 12% in wild-type

• numbers in females are likely higher because numerous deficiet female animals could not be analyzed due to high autolysis

• 17/49 homozygotes exhibit splenomegaly

• 21/49 show perivascular leukocytic infiltration in the kidney

• in males, 19% show glomerulonephritis compared to 0% of wild-type; 31% of female heterozygotes show glomerulonephritis compared to 12% in wild-type

• numbers in females are likely higher because numerous deficiet female animals could not be analyzed due to high autolysis

• after injection of cisplatin, mortality of null mice at days 3-4 is significantly reduced compared to wild-type

• knockouts have decreased creatinine levels (0.9 mg/dl) compared to wild-type (2.7 mg/dl)

• knockouts have decreased BUN levels (125 mg/dl) compared to wild-type (250 mg/dl)

• after injection of cisplatin, mortality of null mice at days 3-4 is significantly reduced compared to wild-type

• Background Sensitivity: on a CD-1 background mice do not develop lupus but Dnase1-deficient mice on a 129 x C57BL/6 background do

• in null mice, no apoptotic bodies are observed while some are found in wild-type mice

• DNA fragmentation is significantly decreased in null mice after cisplatin treatment compared to wild-type mouse tissue

• necrosis is significantly decreased in Dnase1-null mice compared to wild-type after cisplatin treatment

• at day 4, wild-type mice show marked kidney failure, whereas knockouts are significantly protected

• in null mice, no apoptotic bodies are observed while some are found in wild-type mice

• DNA fragmentation is significantly decreased in null mice after cisplatin treatment compared to wild-type mouse tissue

• some heterozygotes display symptoms of systemic lupus erythematosus at 6-8 months of age and die

• 10/66 heterozygotes exhibi splenomegaly

• mice show anti-nuclear antibodies

• 48% of male mice and 65% of female mice display anti-nuclear antibodies compared to 15% of male and 35% of wild-type mice

• 24/66 show perivascular leukocytic infiltration in the kidney

• in males, 15% show glomerulonephritis compared to 0% of wild-type; 19% of female heterozygotes show glomerulonephritis compared to 12% in wild-type

• 10/66 heterozygotes exhibi splenomegaly

• 24/66 show perivascular leukocytic infiltration in the kidney

• in males, 15% show glomerulonephritis compared to 0% of wild-type; 19% of female heterozygotes show glomerulonephritis compared to 12% in wild-type