Mouse Genome Informatics
ht
    Airetm1Mand/Aire+
NOD.129P2-Airetm1Mand
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
immune system
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi) (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)
• chemokines CXCL10, CCL2, and CCL5 are upregulated in sciatic nerves
• 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)
• presence of autoantibodies in the sciatic nerve; autoantibodies are specific for myelin protein zero (P0)
• 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
• nerve infiltrates frequently consist of CD4+ Th cells and F4/80+ macrophages
• 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
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• insulitis occurs in female mice without severe pancreatitis
• 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
• 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
• clasping of hind limbs indicates bilateral weakness
• 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 (J:188686)
• diabetic mutants maintained on insulin rarely develop neuropathy (J:188686)
• 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
• 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
• about 80% of females develop spontaneous autoimmune neuropathy by 22 weeks of age (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)
• 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
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• insulitis occurs in female mice without severe pancreatitis
• 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

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

digestive/alimentary system
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands

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

hematopoietic system
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi) (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
OMIM IDRef(s)
Guillain-Barre Syndrome, Familial; GBS 139393 J:188686