Phenotypes Associated with This Genotype

Genotype
MGI:3803013

• Allelic Composition: Mta2^tm1.1Yzha/Mta2^tm1.1Yzha
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/N

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

Adult Mta2^tm1.1Yzha/Mta2^tm1.1Yzha mice exhibit autoimmunity-related phenotypes in multiple organs

mortality/aging

decreased survivor rate ( J:137101 )

• fewer than 50% of mice survive into adulthood

premature death ( J:137101 )

• mice exhibit a shorter than normal life span that is shorter in female mice than in male mice

perinatal lethality, incomplete penetrance ( J:137101 )

• about half of mice exhibit embryonic or perinatal lethality

embryonic lethality, incomplete penetrance ( J:137101 )

• about half of mice exhibit embryonic or perinatal lethality

• Background Sensitivity: embryonic lethality is more severe on a C57BL/6 background

immune system

panniculitis ( J:137101 )

• mice exhibit dermal and subcutaneous inflammation (panniculitis)

increased T cell proliferation ( J:137101 )

• hyperproliferation follows stimulation with antiCD3 or anti-CD3 and anti-CD8 antibodies

• CD4+CD25- peripheral T cells exhibit hyperproliferation

increased circulating interferon-gamma level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased circulating interleukin-2 level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased circulating interleukin-4 level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased susceptibility to systemic lupus erythematosus ( J:137101 )

• mice exhibit increased susceptibility to systemic lupus erythematosus that can be transferred by bone marrow transplant

increased autoantibody level ( J:137101 )

• mice exhibit an increase in anti-dsDNA, anti-SM. anti-SSA(Ro) and anti-SSB(La) autoantibodies compared to in wild-type mice

increased anti-double stranded DNA antibody level ( J:137101 )

liver inflammation ( J:137101 )

• in more than half of mice and generally limited to the portal regions

glomerulonephritis ( J:137101 )

• some mice exhibit lymphocyte-rich chronic inflammatory cell infiltration

skin inflammation ( J:137101 )

• chronic

dermatitis ( J:137101 )

• chronic spongiotic dermatitis

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:137101 )

N • despite an increase in alanine transaminase levels, the level of aspartate aminotransferase and alkaline phosphatase levels are normal

increased circulating interferon-gamma level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased circulating interleukin-2 level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased circulating interleukin-4 level ( J:137101 )

• following stimulation with or anti-CD3 and anti-CD8 antibodies and under Th2 conditions

increased circulating alanine transaminase level ( J:137101 )

increased urine protein level ( J:137101 )

• 40% of mice exhibit moderate or high urine protein levels with female mice exhibiting a more severe phenotype than male mice

renal/urinary system

increased mesangial cell number ( J:137101 )

• mice exhibit global mesangial cell proliferation in the kidney

increased kidney cell proliferation ( J:137101 )

• mice exhibit global mesangial cell proliferation in the kidney

increased urine protein level ( J:137101 )

• 40% of mice exhibit moderate or high urine protein levels with female mice exhibiting a more severe phenotype than male mice

glomerulonephritis ( J:137101 )

• some mice exhibit lymphocyte-rich chronic inflammatory cell infiltration

reproductive system

female infertility ( J:137101 )

♀

liver/biliary system

liver inflammation ( J:137101 )

• in more than half of mice and generally limited to the portal regions

skeleton

abnormal axial skeleton morphology ( J:137101 )

craniofacial

abnormal craniofacial morphology ( J:137101 )

growth/size/body

decreased body size ( J:137101 )

• body size is two-thirds of normal prior to weaning and after reaching maturity

hematopoietic system

increased T cell proliferation ( J:137101 )

• hyperproliferation follows stimulation with antiCD3 or anti-CD3 and anti-CD8 antibodies

• CD4+CD25- peripheral T cells exhibit hyperproliferation

integument

panniculitis ( J:137101 )

• mice exhibit dermal and subcutaneous inflammation (panniculitis)

skin inflammation ( J:137101 )

• chronic

dermatitis ( J:137101 )

• chronic spongiotic dermatitis

decreased hair follicle number ( J:137101 )

• in some areas mice exhibit immature and decreased hair follicles

• however, frank alopecia is not observed

hyperkeratosis ( J:137101 )

acanthosis ( J:137101 )

skin lesions ( J:137101 )

• mice exhibit periorbital erosion

• from 4 months of age, 75% of mice exhibit skin lesions around the mouth and nose whole 30% of mice exhibit skin lesions on the neck

cellular

increased mesangial cell number ( J:137101 )

• mice exhibit global mesangial cell proliferation in the kidney

increased T cell proliferation ( J:137101 )

• hyperproliferation follows stimulation with antiCD3 or anti-CD3 and anti-CD8 antibodies

• CD4+CD25- peripheral T cells exhibit hyperproliferation

increased kidney cell proliferation ( J:137101 )

• mice exhibit global mesangial cell proliferation in the kidney

adipose tissue

panniculitis ( J:137101 )

• mice exhibit dermal and subcutaneous inflammation (panniculitis)

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:137101