Mouse Genome Informatics
hm1
     Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
premature death ( J:92264 )
• median survival time is around 6 months with about 60% of the deaths due to circulatory failure
• survival time for homozygotes born from heterozygous mothers is shorter than that of homozygotes born from homozygous mothers

cardiovascular system
abnormal myocardial fiber morphology ( J:92264 )
• degeneration of myocytes with edema between the myofibers is seen
cardiomyopathy ( J:92264 )
• mutants that died due to circulatory failure displayed mild to severe cardiomyopathy with 1/3 having a heart 2 to 3 times larger than normal
• cardiomyopathy is not due to increased susceptibility to cardiotoxic viruses
• along with thrombosis one or both atria are enlarged
myocarditis ( J:92264 )
• inflammation of the endothelium extending into the muscle wall is seen in mutant atria

hematopoietic system
enlarged spleen ( J:92264 )
• in less than 10% of older mice enlarged spleens are seen
abnormal spleen B cell follicle morphology ( J:92264 )
• enlarged B-cell follicles are seen
abnormal spleen marginal zone morphology ( J:92264 )
• indistinct marginal zones are seen
thymus cortex hypoplasia ( J:92264 )
• atrophy of the cortical area of the thymus is seen

immune system
myocarditis ( J:92264 )
• inflammation of the endothelium extending into the muscle wall is seen in mutant atria
enlarged spleen ( J:92264 )
• in less than 10% of older mice enlarged spleens are seen
abnormal spleen B cell follicle morphology ( J:92264 )
• enlarged B-cell follicles are seen
abnormal spleen marginal zone morphology ( J:92264 )
• indistinct marginal zones are seen
thymus cortex hypoplasia ( J:92264 )
• atrophy of the cortical area of the thymus is seen
enlarged lymph nodes ( J:92264 )
• in less than 10% of older mice enlarged lymph nodes are seen

liver/biliary system
hepatic necrosis ( J:92264 )
• necrotic areas in the liver are occasionally seen

muscle
abnormal myocardial fiber morphology ( J:92264 )
• degeneration of myocytes with edema between the myofibers is seen
cardiomyopathy ( J:92264 )
• mutants that died due to circulatory failure displayed mild to severe cardiomyopathy with 1/3 having a heart 2 to 3 times larger than normal
• cardiomyopathy is not due to increased susceptibility to cardiotoxic viruses
• along with thrombosis one or both atria are enlarged

renal/urinary system
renal necrosis ( J:92264 )
• necrotic areas in the kidney are occasionally seen

homeostasis/metabolism
atrial thrombosis ( J:92264 )
• thrombus formation is seen in one or both of the atria in mutants that died from circulatory failure

Mouse Models of Human Disease
 OMIM IDRef(s)
Aicardi-Goutieres Syndrome 1; AGS1 225750 J:145466


Mouse Genome Informatics
hm2
     Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging

immune system
immune system phenotype ( J:181257 )
N
• mice exhibit normal levels of antichromatic IgG and anti-dsDNA autoantibodies (J:181257)
increased IgG level ( J:181257 )
• progressive IgG deposition in kidney
increased susceptibility to systemic lupus erythematosus ( J:181257 )
• mice exhibit symptoms of lupus (increased anti-nuclear antigen antibodies, IgG depositions in the kidney and kidney inflammation)
• however, mice exhibit normal levels of antichromatic IgG and anti-dsDNA autoantibodies
increased inflammatory response ( J:181257 )
• in the skeletal muscle, tongue, skin, glandular stomach and heart
• however, mice do not exhibit inflammation in the brain, colon, small intestine, pancreas, lung and liver
myocarditis ( J:181257 )
• mice exhibit regions of lymphohistiocytic, degenerative, and ,in severally affected mice, fibrosing myocarditis
• myocarditis is more severe near the endocardial surface
stomach inflammation ( J:181257 )
• in the glandular stomach with chronic lymphoid aggregates within the mucosa and moderate proliferative gastritis
folliculitis ( J:181257 )
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle
myositis ( J:181257 )
• lymphohistiocytic and degenerative to fibrosing myositis in the skeletal muscle and tongue
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle
glomerulonephritis ( J:181257 )
• mice exhibit mild membranoproliferative glomerulonephritis with hypersegmentation, expanded mesangial matrix and increased cellularity with immune cell infiltrates
dermatitis ( J:181257 )
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle

renal/urinary system
glomerulonephritis ( J:181257 )
• mice exhibit mild membranoproliferative glomerulonephritis with hypersegmentation, expanded mesangial matrix and increased cellularity with immune cell infiltrates

cardiovascular system
myocarditis ( J:181257 )
• mice exhibit regions of lymphohistiocytic, degenerative, and ,in severally affected mice, fibrosing myocarditis
• myocarditis is more severe near the endocardial surface

digestive/alimentary system
stomach inflammation ( J:181257 )
• in the glandular stomach with chronic lymphoid aggregates within the mucosa and moderate proliferative gastritis

integument
folliculitis ( J:181257 )
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle
dermatitis ( J:181257 )
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle

muscle
myositis ( J:181257 )
• lymphohistiocytic and degenerative to fibrosing myositis in the skeletal muscle and tongue
• mild to moderate lymphohistiocytic dermatitis, perifolliculitis and myositis on the muzzle


Mouse Genome Informatics
cx3
     Tcratm1Mom/Tcratm1Mom
Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
mortality/aging ( J:181257 )
N
• mortality observed in either single homozygote is rescued (J:181257)

immune system
immune system phenotype ( J:181257 )
N
• autoimmune pathology observed in Trex1tm1Tld homozygotes is rescued (J:181257)
increased inflammatory response ( J:181257 )
• as in Tcratm1Mom homozygotes
colitis ( J:181257 )
• inflammatory bowel disease as in Tcratm1Mom homozygotes
myositis ( J:181257 )
• as in Tcratm1Mom homozygotes
skin inflammation ( J:181257 )
• as in Tcratm1Mom homozygotes

digestive/alimentary system
colitis ( J:181257 )
• inflammatory bowel disease as in Tcratm1Mom homozygotes

integument
skin inflammation ( J:181257 )
• as in Tcratm1Mom homozygotes

muscle
myositis ( J:181257 )
• as in Tcratm1Mom homozygotes


Mouse Genome Informatics
cx4
     Ighmtm1Cgn/Ighmtm1Cgn
Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
premature death ( J:181257 )
• compared with Ighmtm1Cgn homozygotes
• however, the premature death observed in Trex1tm1Tld homozygotes is rescued

immune system
increased inflammatory response ( J:181257 )
• as in Trex1tm1Tld homozygotes
myocarditis ( J:181257 )
• as in Trex1tm1Tld homozygotes
kidney inflammation ( J:181257 )
• as in Trex1tm1Tld homozygotes
tubular nephritis ( J:181257 )
• unlike in Trex1tm1Tld homozygotes

renal/urinary system
renal/urinary system phenotype ( J:181257 )
N
• unlike Trex1tm1Tld homozygotes, mice do not exhibit glomerular lesions (J:181257)
kidney inflammation ( J:181257 )
• as in Trex1tm1Tld homozygotes
tubular nephritis ( J:181257 )
• unlike in Trex1tm1Tld homozygotes

cardiovascular system
cardiac fibrosis ( J:181257 )
• as in Trex1tm1Tld homozygotes
myocarditis ( J:181257 )
• as in Trex1tm1Tld homozygotes


Mouse Genome Informatics
cx5
     Mavstm1Itl/Mavstm1Itl
Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
premature death ( J:181257 )
• as in Trex1tm1Tld homozygotes

immune system
increased inflammatory response ( J:181257 )
• in the skeletal muscle, tongue, skin, glandular stomach and heart as in Trex1tm1Tld homozygotes

cardiovascular system

digestive/alimentary system

integument

muscle


Mouse Genome Informatics
cx6
     Tmem173tm1Gnb/Tmem173tm1Gnb
Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
mortality/aging ( J:181257 )
N
• mice exhibit normal survival unlike Trex1tm1Tld homozygotes (J:181257)

immune system
immune system phenotype ( J:181257 )
N
• mice do not exhibit multi-organ inflammation unlike Trex1tm1Tld homozygotes (J:181257)


Mouse Genome Informatics
cx7
     Rag2tm1.1Cgn/Rag2tm1.1Cgn
Trex1tm1Tld/Trex1tm1Tld
involves: 129P2/OlaHsd * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
mortality/aging ( J:181257 )
N
• autoimmune pathology and mortality observed in Trex1tm1Tld homozygotes are rescued regardless of hematopoietic reconstitution with bone marrow from Ifnar1tm1Agt homozygotes (J:181257)

immune system
immune system phenotype ( J:181257 )
N
• autoimmune pathology and mortality observed in Trex1tm1Tld homozygotes are rescued regardless of hematopoietic reconstitution with bone marrow from Ifnar1tm1Agt homozygotes (J:181257)