Mouse Genome Informatics
cx
    Psen1tm1Bdes/Psen1+
Psen2tm1Bdes/Psen2tm1Bdes

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
immune system
• an increase in the CD4+/CD8+ ratio
• severe leukocytosis
• 3-fold increase in spleen weight/body weight ratio
• hypergammaglobulinemia; immunoglobulin deposits are seen along the basal lamina and in the subjacent connective tissue
• enlarged lymph nodes result in the swelling of the ventrolateral neck
• develop an autoimmune phenotype in late adulthood (after 6 months of age) exhibiting features of systemic lupus erythematosus
• increase in levels of anti-ssDNA IgG antibody levels
• mutants exhibit increased concentration of serum gamma-globulins and alpha1-globulins and a decrease of albumin
• leukocyte invasions and Ig deposits are seen in the skin and kidney, and to a lesser extent in liver, skeletal muscle and salivary glands, most often associated with blood vessels and stroma and less so with the parenchyma
• arteries in most tissues, but especially in skin and kidney, are surrounded and invaded by leukocytes, similar to that seen in human leukocytoclastic autoimmune vasculitis
• variable severity of keratitis: dense leukocyte infiltrates are concentrated in the outer half of the corneal stroma, which is thickened and vascularized
• leukocyte aggregates are mostly in the vicinity of larger blood vessles and also invade the glomerula of the parenchyma; Ig deposits are also seen in the glomerula
• skin of aged mutants has multifocal invasion of corium and subcutis by leukocytes (predominantly lymphocytes), often forming large nodular aggregates
• inflammation involves a mixed population of cells consisting of B- and T-lymphocytes and macrophages

vision/eye
• variable severity of keratitis: dense leukocyte infiltrates are concentrated in the outer half of the corneal stroma, which is thickened and vascularized
• sometimes the epithelium exhibits focal dysplasia characterized by an irregular thickening and a loss of its normal stratification

renal/urinary system
• low-level microproteinuria
• low-level microhematuria
• leukocyte aggregates are mostly in the vicinity of larger blood vessles and also invade the glomerula of the parenchyma; Ig deposits are also seen in the glomerula

cardiovascular system
• arteries in most tissues, but especially in skin and kidney, are surrounded and invaded by leukocytes, similar to that seen in human leukocytoclastic autoimmune vasculitis

hematopoietic system
• an increase in the CD4+/CD8+ ratio
• severe leukocytosis
• 3-fold increase in spleen weight/body weight ratio
• hypergammaglobulinemia; immunoglobulin deposits are seen along the basal lamina and in the subjacent connective tissue

homeostasis/metabolism
• low-level microproteinuria
• low-level microhematuria

integument
• skin of aged mutants has multifocal invasion of corium and subcutis by leukocytes (predominantly lymphocytes), often forming large nodular aggregates
• inflammation involves a mixed population of cells consisting of B- and T-lymphocytes and macrophages
• skin contains numerous intraepithelial keratin 'horn' cysts and a highly papillomatotic interface to the underlying corium
• skin lesions resemble human seborrheic keratosis
• 75% of mutants aged between 6 and 18 months of age develop wart-like protrusions and exulcerations of the skin
• 75% of mutants aged between 6 and 18 months of age develop exulcerations of the skin
• skin develops numerous intraepithelial keratin 'horn' cysts in late adulthood (after 6 months of age)

Mouse Models of Human Disease
OMIM IDRef(s)
Keratosis, Seborrheic 182000 J:91235
Systemic Lupus Erythematosus; SLE 152700 J:91235