Phenotypes Associated with This Genotype

Genotype
MGI:3803199

• Allelic Composition: Aire^tm1Mand/Aire⁺
• Genetic Background: NOD.129P2-Aire^tm1Mand

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

immune system

abnormal CD4-positive, alpha-beta T cell physiology ( J:135154 , J:188686 )

• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62L^lo CD44^hi) (J:135154)

• mutants show an increase in IFN-gamma producing CD4+ T cells within sciatic nerves and the spleen, indicating a Th1 effector response (J:188686)

abnormal chemokine level ( J:188686 )

• chemokines CXCL10, CCL2, and CCL5 are upregulated in sciatic nerves

increased CXCL10 level ( J:188686 )

• CXCL10 is upregulated in sciatic nerves

increased susceptibility to autoimmune diabetes ( J:135154 , J:188686 )

• diabetes mellitus occurs in females at an incidence rate (20%) similar to that observed in the NOD strain with wild-type Aire alleles (J:135154)

increased autoantibody level ( J:188686 )

• presence of autoantibodies in the sciatic nerve; autoantibodies are specific for myelin protein zero (P0)

increased inflammatory response ( J:188686 )

• nerve infiltrates frequently consist of CD4+ Th cells and F4/80+ macrophages

• immune cell (mononuclear) infiltration into sciatic nerves, but not in brain or spinal cord

• while a previous study found that mice either develop diabetes or neuropathy, in this study mice with both diabetes and neuropathy are seen on a rare occasion and they exhibit moderate immune infiltration in the sciatic nerves

• mutants show an increase in IFN-gamma producing CD4+ T cells within sciatic nerves and the spleen, indicating a Th1 effector response

• mutants with spontaneous autoimmune diabetes that do not develop neuropathy do not show immune infiltration in the sciatic nerve

salivary gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands

thyroid gland inflammation ( J:135154 )

• severe thyroiditis is observed in mice 25 to 30 weeks in age

• some mice have complete obliteration of the thyroid follicles

• 25% of mice have at least half of their thyroid gland effaced

lacrimal gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands

chronic pancreas inflammation ( J:135154 )

• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas

insulitis ( J:135154 )

• insulitis occurs in female mice without severe pancreatitis

CNS inflammation ( J:135154 )

• lymphocytic infiltration of the CNS leads to hind limb paralysis by 22 weeks of age in 80% of mice

• mice develop either diabetes or neuropathy but are never observed having both conditions

behavior/neurological

limb grasping ( J:188686 )

• clasping of hind limbs indicates bilateral weakness

paralysis ( J:188686 )

♀ • about 80% of females develop spontaneous autoimmune neuropathy by 22 weeks of age, displaying bilateral weakness of the hind limbs that progresses to severe paralysis affecting all limbs

♀ • diabetic mutants maintained on insulin rarely develop neuropathy

hindlimb paralysis ( J:135154 )

• progressive peripheral neuropathy results in hind limb paralysis by beginning at 17 weeks of age

• over 80% of mice exhibit this neuropathy by 22 weeks of age

• mice develop either diabetes or neuropathy but are never observed having both conditions

nervous system

CNS inflammation ( J:135154 )

• lymphocytic infiltration of the CNS leads to hind limb paralysis by 22 weeks of age in 80% of mice

• mice develop either diabetes or neuropathy but are never observed having both conditions

abnormal nervous system morphology ( J:188686 )

♀ • about 80% of females develop spontaneous autoimmune neuropathy by 22 weeks of age

abnormal sciatic nerve morphology ( J:135154 , J:188686 )

• lymphocytic infiltration occurs in the sciatic nerve of mice that have hind limb paralysis (J:135154)

• immune cell (mononuclear) infiltration into sciatic nerves, but not in brain or spinal cord (J:188686)

• multifocal areas of demyelination in the sciatic nerve (J:188686)

demyelination ( J:188686 )

• multifocal areas of demyelination in the sciatic nerve and demyelination of individual axons are seen

• a decrease in density of myelinated axons is seen in the sciatic nerve of neuropathic mutants

endocrine/exocrine glands

salivary gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands

thyroid gland inflammation ( J:135154 )

• severe thyroiditis is observed in mice 25 to 30 weeks in age

• some mice have complete obliteration of the thyroid follicles

• 25% of mice have at least half of their thyroid gland effaced

lacrimal gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands

chronic pancreas inflammation ( J:135154 )

• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas

insulitis ( J:135154 )

• insulitis occurs in female mice without severe pancreatitis

vision/eye

lacrimal gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands

digestive/alimentary system

salivary gland inflammation ( J:135154 )

• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands

homeostasis/metabolism

abnormal chemokine level ( J:188686 )

• chemokines CXCL10, CCL2, and CCL5 are upregulated in sciatic nerves

increased CXCL10 level ( J:188686 )

• CXCL10 is upregulated in sciatic nerves

hematopoietic system

abnormal CD4-positive, alpha-beta T cell physiology ( J:135154 , J:188686 )

• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62L^lo CD44^hi) (J:135154)

• mutants show an increase in IFN-gamma producing CD4+ T cells within sciatic nerves and the spleen, indicating a Th1 effector response (J:188686)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Guillain-Barre syndrome		DOID:12842	OMIM:139393	J:188686