Phenotypes associated with this allele

• Allele Symbol: Zfp36^tm1Pjb
• Allele Name: targeted mutation 1, Perry J Blackshear
• Allele ID: MGI:2652418
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Zfp36^tm1Pjb/Zfp36^tm1Pjb	B6.Cg-Zfp36^tm1Pjb	MGI:3037334
hm2	Zfp36^tm1Pjb/Zfp36^tm1Pjb	Not Specified	MGI:2652466
cx3	Tia1^tm1Andp/Tia1^tm1Andp Zfp36^tm1Pjb/Zfp36^tm1Pjb	B6.Cg-Tia1^tm1Andp Zfp36^tm1Pjb	MGI:3037328
cx4	Tnf^tm3Gkl/Tnf^tm3Gkl Zfp36^tm1Pjb/Zfp36^tm1Pjb	involves: 129S/SvEv * C57BL/6	MGI:3692748
cx5	Tnf^tm1Gkl/Tnf^tm1Gkl Zfp36^tm1Pjb/Zfp36^tm1Pjb	involves: 129S/SvEv * C57BL/6	MGI:5588803

Genotype
MGI:3037334

hm1

• Allelic Composition: Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: B6.Cg-Zfp36^tm1Pjb

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

immune system

blood vessel inflammation ( J:214114 )

• increase in pro-inflammatory and atherosclerosis marker gene expression in aortas indicating vascular inflammation

increased granulocyte number ( J:214114 )

• slight enhancement in the blood

increased neutrophil cell number ( J:214114 )

• slight enhancement in the blood

decreased lymphocyte cell number ( J:214114 )

• decrease in lymphocyte cell numbers

increased monocyte cell number ( J:214114 )

• slight enhancement in the blood

abnormal macrophage physiology ( J:88443 )

• in macrophages from double homozygotes lipopolysaccharide-induced expression of TNF- alpha is significantly increased

autoimmune arthritis ( J:88443 )

• homozygotes develop severe arthritis

• finger joints from double homozygotes display inflammatory pannus and bony erosions

skeleton

autoimmune arthritis ( J:88443 )

• homozygotes develop severe arthritis

• finger joints from double homozygotes display inflammatory pannus and bony erosions

hematopoietic system

increased granulocyte number ( J:214114 )

• slight enhancement in the blood

increased neutrophil cell number ( J:214114 )

• slight enhancement in the blood

thrombocytosis ( J:214114 )

• slight enhancement in the blood

decreased lymphocyte cell number ( J:214114 )

• decrease in lymphocyte cell numbers

increased monocyte cell number ( J:214114 )

• slight enhancement in the blood

abnormal macrophage physiology ( J:88443 )

• in macrophages from double homozygotes lipopolysaccharide-induced expression of TNF- alpha is significantly increased

cardiovascular system

decreased systemic arterial blood pressure ( J:214114 )

• reduction in blood pressure

abnormal vasodilation ( J:214114 )

• aortas are less responsive to acetylcholine-induced relaxation mice however show similar relaxation responses to the NOS inhibitor L-NAME and to the NO-donor sodium nitroprusside

blood vessel inflammation ( J:214114 )

• increase in pro-inflammatory and atherosclerosis marker gene expression in aortas indicating vascular inflammation

cellular

increased cellular sensitivity to oxidative stress ( J:214114 )

• mice show higher reactive oxygen and nitrogen species (RONS) formation in the presence of NADPH in cardiac membrane fractions, indicating enhanced burden of oxidative stress

oxidative stress ( J:214114 )

• mice show higher reactive oxygen and nitrogen species (RONS) formation under PDBu-stimulated conditions in whole blood, indicating enhanced burden of oxidative stress

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:214114 )

N • mice show normal blood cholesterol, triglyceride and glucose levels

abnormal nitric oxide homeostasis ( J:214114 )

• marker analysis indicates reduced NO bioavailability

muscle

abnormal vasodilation ( J:214114 )

• aortas are less responsive to acetylcholine-induced relaxation mice however show similar relaxation responses to the NOS inhibitor L-NAME and to the NO-donor sodium nitroprusside

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rheumatoid arthritis		DOID:7148	OMIM:180300	J:214114

Genotype
MGI:2652466

hm2

• Allelic Composition: Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: Not Specified

mortality/aging

premature death ( J:33986 )

• 34% died prior to 7 mo of age

adipose tissue

absent subcutaneous adipose tissue ( J:33986 )

growth/size/body

decreased body weight ( J:33986 )

postnatal growth retardation ( J:33986 )

• reduced rate of weight gain exhibited by all mice between 1 and 8 wks of age

enlarged spleen ( J:33986 )

• 41% increase in size relative to wild-type

spleen hyperplasia ( J:33986 )

hematopoietic system

abnormal thymus cortex morphology ( J:33986 )

• disorganized

abnormal thymus medulla morphology ( J:33986 )

• disorganized

thymus hypoplasia ( J:33986 )

• 50% reduction in size relative to wild-type by 4 days of age

enlarged spleen ( J:33986 )

• 41% increase in size relative to wild-type

spleen hyperplasia ( J:33986 )

extramedullary hematopoiesis ( J:33986 )

increased leukocyte cell number ( J:33986 )

• increased number of neutrophils in the peripheral blood, spleen, and bone marrow, but normal peripheral erythrocyte, hemoglobin, hematocrit, and platelet counts

immune system

heart inflammation ( J:33986 )

• 1 mouse exhibited inflammation of the interventricular septum

abnormal thymus cortex morphology ( J:33986 )

• disorganized

abnormal thymus medulla morphology ( J:33986 )

• disorganized

thymus hypoplasia ( J:33986 )

• 50% reduction in size relative to wild-type by 4 days of age

enlarged spleen ( J:33986 )

• 41% increase in size relative to wild-type

spleen hyperplasia ( J:33986 )

increased leukocyte cell number ( J:33986 )

• increased number of neutrophils in the peripheral blood, spleen, and bone marrow, but normal peripheral erythrocyte, hemoglobin, hematocrit, and platelet counts

enlarged lymph nodes ( J:33986 )

conjunctivitis ( J:33986 )

• displayed by 72% of mice surviving to 7 mo age

autoimmune arthritis ( J:33986 )

• displayed by 88% of mice surviving to 7 mo age

liver inflammation ( J:33986 )

• necrotizing hepatitis

dermatitis ( J:33986 )

• displayed by 68% of mice surviving to 7 mo age

renal/urinary system

abnormal renal glomerulus morphology ( J:33986 )

• increased cellularity of glomeruli

• focal segmental thickening of peripheral capillary loops

skeleton

autoimmune arthritis ( J:33986 )

• displayed by 88% of mice surviving to 7 mo age

vision/eye

conjunctivitis ( J:33986 )

• displayed by 72% of mice surviving to 7 mo age

cardiovascular system

heart inflammation ( J:33986 )

• 1 mouse exhibited inflammation of the interventricular septum

liver/biliary system

liver inflammation ( J:33986 )

• necrotizing hepatitis

integument

absent subcutaneous adipose tissue ( J:33986 )

dermatitis ( J:33986 )

• displayed by 68% of mice surviving to 7 mo age

alopecia ( J:33986 )

endocrine/exocrine glands

abnormal thymus cortex morphology ( J:33986 )

• disorganized

abnormal thymus medulla morphology ( J:33986 )

• disorganized

thymus hypoplasia ( J:33986 )

• 50% reduction in size relative to wild-type by 4 days of age

Genotype
MGI:3037328

cx3

• Allelic Composition: Tia1^tm1Andp/Tia1^tm1Andp; Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: B6.Cg-Tia1^tm1Andp Zfp36^tm1Pjb

growth/size/body

postnatal growth retardation ( J:88443 )

• double homozygotes are small at birth and grow slowly

hematopoietic system

increased neutrophil cell number ( J:88443 )

• significant increases in neutrophils are found in the bone marrow and peripheral blood

abnormal macrophage physiology ( J:88443 )

• in macrophages from double homozygotes lipopolysaccharide-induced expression of TNF- alpha is significantly increased

immune system

increased neutrophil cell number ( J:88443 )

• significant increases in neutrophils are found in the bone marrow and peripheral blood

abnormal macrophage physiology ( J:88443 )

• in macrophages from double homozygotes lipopolysaccharide-induced expression of TNF- alpha is significantly increased

autoimmune arthritis ( J:88443 )

• double homozygotes develop arthritis that is more severe than that seen in either single homozygote

• finger joints from double homozygotes display inflammatory pannus and bony erosions

skeleton

autoimmune arthritis ( J:88443 )

• double homozygotes develop arthritis that is more severe than that seen in either single homozygote

• finger joints from double homozygotes display inflammatory pannus and bony erosions

Genotype
MGI:3692748

cx4

• Allelic Composition: Tnf^tm3Gkl/Tnf^tm3Gkl; Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: involves: 129S/SvEv * C57BL/6

immune system

immune system phenotype ( J:114740 )

N • up to 7 months of age, double mutants appear phenotypically normal and lack joint inflammation, cartilage erosion, and pannus formation compared to TNF-sufficient, Zpf36-null littermates which develop joint swelling and cachexia by 7 months

myeloid hyperplasia ( J:114740 )

• double mutants exhibit myeloid hyperplasia, similar to TNF-sufficient, Zpf36-null littermates

hematopoietic system

myeloid hyperplasia ( J:114740 )

• double mutants exhibit myeloid hyperplasia, similar to TNF-sufficient, Zpf36-null littermates

Genotype
MGI:5588803

cx5

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl; Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: involves: 129S/SvEv * C57BL/6

cardiovascular system

abnormal vasodilation ( J:214114 )

• mice do not show improvement of the endothelial dysfunction seen in single Zfp36 homozygotes, with aortas still less responsive to acetylcholine-induced relaxation

cellular

oxidative stress ( J:214114 )

• mice show a partial reduction of the enhanced reactive oxygen and nitrogen species (RONS) formation under PDBu-stimulated conditions in whole blood that is seen in single Zfp36 homozygotes

muscle

abnormal vasodilation ( J:214114 )

• mice do not show improvement of the endothelial dysfunction seen in single Zfp36 homozygotes, with aortas still less responsive to acetylcholine-induced relaxation