Phenotypes associated with this allele

• Allele Symbol: Dnase1^tm1Tmo
• Allele Name: targeted mutation 1, Tarik Moroy
• Allele ID: MGI:2387029
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dnase1^tm1Tmo/Dnase1^tm1Tmo	involves: 129P2/OlaHsd * C57BL/6	MGI:3639668
hm2	Dnase1^tm1Tmo/Dnase1^tm1Tmo	involves: 129P2/OlaHsd * CD-1	MGI:3639676
ht3	Dnase1^tm1Tmo/Dnase1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3639669

Genotype
MGI:3639668

hm1

• Allelic Composition: Dnase1^tm1Tmo/Dnase1^tm1Tmo
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:62549 )

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

immune system

enlarged spleen ( J:62549 )

• 17/49 homozygotes exhibit splenomegaly

increased susceptibility to systemic lupus erythematosus ( J:62549 )

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

increased anti-nuclear antigen antibody level ( J:62549 )

• 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

kidney inflammation ( J:62549 )

• 21/49 show perivascular leukocytic infiltration in the kidney

glomerulonephritis ( J:62549 )

• 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

enlarged spleen ( J:62549 )

• 17/49 homozygotes exhibit splenomegaly

renal/urinary system

kidney inflammation ( J:62549 )

• 21/49 show perivascular leukocytic infiltration in the kidney

glomerulonephritis ( J:62549 )

• 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

growth/size/body

enlarged spleen ( J:62549 )

• 17/49 homozygotes exhibit splenomegaly

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:62549

Genotype
MGI:3639676

hm2

• Allelic Composition: Dnase1^tm1Tmo/Dnase1^tm1Tmo
• Genetic Background: involves: 129P2/OlaHsd * CD-1

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:110060 )

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

homeostasis/metabolism

decreased circulating creatinine level ( J:110060 )

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

decreased blood urea nitrogen level ( J:110060 )

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

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:110060 )

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

immune system

decreased susceptibility to systemic lupus erythematosus ( J:110060 )

• 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

decreased kidney apoptosis ( J:110060 )

• 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

renal tubular necrosis ( J:110060 )

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

kidney failure ( J:110060 )

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

cellular

decreased kidney apoptosis ( J:110060 )

• 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

Genotype
MGI:3639669

ht3

• Allelic Composition: Dnase1^tm1Tmo/Dnase1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:62549 )

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

immune system

enlarged spleen ( J:62549 )

• 10/66 heterozygotes exhibi splenomegaly

increased anti-nuclear antigen antibody level ( J:62549 )

• 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

kidney inflammation ( J:62549 )

• 24/66 show perivascular leukocytic infiltration in the kidney

glomerulonephritis ( J:62549 )

• 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

enlarged spleen ( J:62549 )

• 10/66 heterozygotes exhibi splenomegaly

renal/urinary system

kidney inflammation ( J:62549 )

• 24/66 show perivascular leukocytic infiltration in the kidney

glomerulonephritis ( J:62549 )

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

growth/size/body

enlarged spleen ( J:62549 )

• 10/66 heterozygotes exhibi splenomegaly