Mouse Genome Informatics
hm1
    Dnase1tm1Tmo/Dnase1tm1Tmo
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some homozygotes display symptoms of systemic lupus erythematosus at 6-8 months of age and die

immune system
• 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

hematopoietic system
• 17/49 homozygotes exhibit splenomegaly

renal/urinary system
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus; SLE 152700 J:62549


Mouse Genome Informatics
hm2
    Dnase1tm1Tmo/Dnase1tm1Tmo
involves: 129P2/OlaHsd * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• after injection of cisplatin, mortality of null mice at days 3-4 is significantly reduced compared to wild-type

homeostasis/metabolism
• 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

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

renal/urinary system
• 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

cellular
• 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


Mouse Genome Informatics
ht3
    Dnase1tm1Tmo/Dnase1+
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some heterozygotes display symptoms of systemic lupus erythematosus at 6-8 months of age and die

immune system
• 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

hematopoietic system
• 10/66 heterozygotes exhibi splenomegaly

renal/urinary system
• 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