Phenotypes associated with this allele

• Allele Symbol: Il1rn^tm1Nick
• Allele Name: targeted mutation 1, Martin J H Nicklin
• Allele ID: MGI:3038876
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il1rn^tm1Nick/Il1rn^tm1Nick	involves: 129P2/OlaHsd * MF1	MGI:3039882
hm2	Il1rn^tm1Nick/Il1rn^tm1Nick	involves: 129P2/OlaHsd * MF1 * BALB/cAnNHsd	MGI:3039918
hm3	Il1rn^tm1Nick/Il1rn^tm1Nick	involves: BALB/cAnNHsd	MGI:3039920
hm4	Il1rn^tm1Nick/Il1rn^tm1Nick	involves: BALB/cAnNHsd * C57BL/6	MGI:3039922
hm5	Il1rn^tm1Nick/Il1rn^tm1Nick	involves: C57BL/6	MGI:3039921
ht6	Il1rn^tm1Nick/Il1rn^+	involves: 129P2/OlaHsd * MF1	MGI:3039889

Genotype
MGI:3039882

hm1

• Allelic Composition: Il1rn^tm1Nick/Il1rn^tm1Nick
• Genetic Background: involves: 129P2/OlaHsd * MF1

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

mortality/aging

premature death ( J:59410 )

• death due to vessel wall collapse, stenosis, and organ infarction or from hemorrhage from ruptured aneurysms

• mice either died spontaneously or were euthanized by 159 days (median)

cardiovascular system

artery stenosis ( J:59410 )

• collapse and stenosis of inflamed arteries, putatively due to destruction of the elastic laminae

aneurysm ( J:59410 )

• aneurysms were observed in some mice, putatively due to destruction of the elastic laminae

aortitis ( J:59410 )

• arterial inflammation involving high stress points, including branch points and flexures of the aorta and its primary and secondary branches

• repaired regions which showed damaged elastic layers and fibrous scarring but no inflammatory infiltrate were observed

• lesions were not observed in veins, capillaries, or in smaller arteries

immune system

aortitis ( J:59410 )

• arterial inflammation involving high stress points, including branch points and flexures of the aorta and its primary and secondary branches

• repaired regions which showed damaged elastic layers and fibrous scarring but no inflammatory infiltrate were observed

• lesions were not observed in veins, capillaries, or in smaller arteries

chronic inflammation ( J:59410 )

• histologic examination of inflamed arteries revealed a characteristic whorled pattern of inflammatory infiltrate and leukocytes

• massive transmural infiltration of neutrophils, macrophages, and CD4⁺ T cells

• CD19⁺ B cells and CD8⁺ T cells were rarely detected in the arterial infiltrate

Genotype
MGI:3039918

hm2

• Allelic Composition: Il1rn^tm1Nick/Il1rn^tm1Nick
• Genetic Background: involves: 129P2/OlaHsd * MF1 * BALB/cAnNHsd

immune system

immune system phenotype ( J:89034 )

N • none of the F2 homozygotes (median age 211 days) exhibit joint inflammation (limb swelling)

N • Background Sensitivity: on a mixed background involving 129 and MF1, homozygotes develop arteritis (89%) but not arthritis or cutaneous inflammation, while on a C57BL/6 background homozygotes do not develop any of these diseases

aortitis ( J:89034 )

• at least 2 of 7 homozygotes (F2, median age 211 days) display arteritis at the aortic root

skin inflammation ( J:89034 )

• 5 of 7 homozygotes (F2, median age 211 days) display cutaneous inflammation of the ear pinnae, as determined by histology

cardiovascular system

aortitis ( J:89034 )

• at least 2 of 7 homozygotes (F2, median age 211 days) display arteritis at the aortic root

integument

skin inflammation ( J:89034 )

• 5 of 7 homozygotes (F2, median age 211 days) display cutaneous inflammation of the ear pinnae, as determined by histology

Genotype
MGI:3039920

hm3

• Allelic Composition: Il1rn^tm1Nick/Il1rn^tm1Nick
• Genetic Background: involves: BALB/cAnNHsd

immune system

aortitis ( J:89034 )

• 21 of 27 homozygotes (median age 147 days) display arteritis at the aortic root

rheumatoid arthritis ( J:89034 )

• 20 of 27 homozygotes (median age 147 days) display advanced joint swelling

skin inflammation ( J:89034 )

• 64% of homozygotes develop inflammation localized to the skin of the ear pinna

• earliest cases of ear reddening appear at 54 and 59 days of age

• onset of ear pinna inflammation is sporadic

• incidence of ear pinna inflammation appears to rise sharply after 100 days age, affecting 77% of older mice

• 19 of 27 homozygotes (median age 147 days) display ear pinna inflammation

cardiovascular system

aortitis ( J:89034 )

• 21 of 27 homozygotes (median age 147 days) display arteritis at the aortic root

pathological neovascularization ( J:89034 )

• homozygotes display dense patterns of activated small dermal vessels, as shown by an apparently disorganized expression of the constitutive endothelial marker CD31 and abundant E-selectin in severely affected tissue

skeleton

rheumatoid arthritis ( J:89034 )

• 20 of 27 homozygotes (median age 147 days) display advanced joint swelling

integument

skin inflammation ( J:89034 )

• 64% of homozygotes develop inflammation localized to the skin of the ear pinna

• earliest cases of ear reddening appear at 54 and 59 days of age

• onset of ear pinna inflammation is sporadic

• incidence of ear pinna inflammation appears to rise sharply after 100 days age, affecting 77% of older mice

• 19 of 27 homozygotes (median age 147 days) display ear pinna inflammation

abnormal dermal layer morphology ( J:89034 )

• affected homozygotes display large epidermal projections into a grossly thickened dermis and both tissues are infiltrated by leukocytes

• dendritic cells and activated T cells of both helper classes are identified in the dermis

• a high density of macrophages is observed in the dermis, where mast cells are also abundant

• dense patterns of activated small dermal vessels are seen in severely affected dermis

thick dermal layer ( J:89034 )

abnormal epidermal layer morphology ( J:89034 )

• affected homozygotes display a convoluted epidermis with large rete pegs projecting deeply into the dermis

• the epidermis is hypertrophic and infiltrated by activated CD4⁺ T cells of both helper classes, and CD205⁺ or MHCII⁺ dendritic cells

parakeratosis ( J:89034 )

• affected homozygotes display parakeratotsis in the stratum corneum

epidermal desquamation ( J:89034 )

• severely affected homozygotes display sloughed nucleated squames in the stratum corneum

thick epidermis ( J:89034 )

skin lesions ( J:89034 )

• homozygotes frequently develop inflamed and thickened patches on their ear pinnae

psoriasis ( J:89034 )

• nuclei appear to be retained in the outer layer of the stratum corneum, similar to human psoriasis

• homozygotes develop psoriasis-like lesions in their ear pinnae

• the disease is generally symmetrical; other areas of the body are infrequently involved

• neutrophil-rich microabscesses are observed beneath the stratum corneum in severely affected skin, similar to human psoriasis

• mast cells are frequently observed in the affected dermis, similar to human psoriasis

• CD3⁺ and CD4⁺ cells are abundant in affected (psoriasiform) epidermis and dermis

• dendritic cells and activated T cells of both helper classes are identified in the dermis

• IL-1beta expression is abundant in affected dermis where a high density of macrophages is observed

abnormal keratinocyte physiology ( J:89034 )

• immature keratin (K6) expression is abnormally extended throughout the expanded subcorneal layers of affected tissue, suggesting keratinocyte activation

Genotype
MGI:3039922

hm4

• Allelic Composition: Il1rn^tm1Nick/Il1rn^tm1Nick
• Genetic Background: involves: BALB/cAnNHsd * C57BL/6

cardiovascular system

aortitis ( J:89034 )

• 6 of 14 homozygotes (F2, median age 200 days) display arteritis at the aortic root

immune system

immune system phenotype ( J:89034 )

N • none of the F1 or F2 homozygotes (median age 200 days) exhibit cutaneous inflammation of the ear pinnae

aortitis ( J:89034 )

• 6 of 14 homozygotes (F2, median age 200 days) display arteritis at the aortic root

rheumatoid arthritis ( J:89034 )

• only 7 of 95 homozygotes (F2, median age 200 days) display joint inflammation (limb swelling)

skeleton

rheumatoid arthritis ( J:89034 )

• only 7 of 95 homozygotes (F2, median age 200 days) display joint inflammation (limb swelling)

Genotype
MGI:3039921

hm5

• Allelic Composition: Il1rn^tm1Nick/Il1rn^tm1Nick
• Genetic Background: involves: C57BL/6

immune system

immune system phenotype ( J:89034 )

N • homozygotes (median age 202 days) exhibit no cutaneous inflammation of the ear pinnae, as determined by histology

N • neither joint inflammation (limb swelling) nor aorta inflammation is observed

Genotype
MGI:3039889

ht6

• Allelic Composition: Il1rn^tm1Nick/Il1rn⁺
• Genetic Background: involves: 129P2/OlaHsd * MF1

immune system

aortitis ( J:59410 )

• much milder than what was observed in homozygotes

• as in homozygotes, repaired regions which showed damaged elastic layers and fibrous scarring but no inflammatory infiltrate were observed

cardiovascular system

aortitis ( J:59410 )

• much milder than what was observed in homozygotes

• as in homozygotes, repaired regions which showed damaged elastic layers and fibrous scarring but no inflammatory infiltrate were observed