Phenotypes associated with this allele

• Allele Symbol: Psen2^tm1Bdes
• Allele Name: targeted mutation 1, Bart de Strooper
• Allele ID: MGI:2149117
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Psen2^tm1Bdes/Psen2^tm1Bdes	involves: 129P2/OlaHsd * C57BL/6J	MGI:2175000
cx2	Psen1^tm1Bdes/Psen1^+ Psen2^tm1Bdes/Psen2^tm1Bdes	involves: 129P2/OlaHsd	MGI:3702859
cx3	Psen1^tm1Bdes/Psen1^tm1Bdes Psen2^tm1Bdes/Psen2^tm1Bdes	involves: 129P2/OlaHsd * C57BL/6J	MGI:3702892

Genotype
MGI:2175000

hm1

• Allelic Composition: Psen2^tm1Bdes/Psen2^tm1Bdes
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

Phenotypical analysis of Psen2^tm1Bdes/Psen2^tm1Bdes mice

respiratory system

lung hemorrhage ( J:58118 )

• at 3 and 6 months of age, observe hemorrhages within large groups of alveoli and their adjoining airways

increased lung apoptosis ( J:58118 )

• apoptosis is evident in the lung parenchyma, within the vascular endothelium and bronchial epithelium

increased lung endothelial cell apoptosis ( J:58118 )

• apoptosis is evident within the vascular endothelium

increased pulmonary alveolus wall thickness ( J:58118 )

• from 3 months of age, show a thickening of alveolar walls, with broad strands of fibrotic tissues

pulmonary fibrosis ( J:58118 )

• develop mild pulmonary fibrosis with age

cardiovascular system

lung hemorrhage ( J:58118 )

• at 3 and 6 months of age, observe hemorrhages within large groups of alveoli and their adjoining airways

limbs/digits/tail

limbs/digits/tail phenotype ( J:58118 )

N • surprisingly, no alterations in digit formation are seen

nervous system

nervous system phenotype ( J:58118 )

N • surprisingly, no alterations in brain anatomy are seen

cellular

increased lung apoptosis ( J:58118 )

• apoptosis is evident in the lung parenchyma, within the vascular endothelium and bronchial epithelium

increased lung endothelial cell apoptosis ( J:58118 )

• apoptosis is evident within the vascular endothelium

Genotype
MGI:3702859

cx2

• Allelic Composition: Psen1^tm1Bdes/Psen1⁺; Psen2^tm1Bdes/Psen2^tm1Bdes
• Genetic Background: involves: 129P2/OlaHsd

immune system

enlarged spleen ( J:91235 )

• 3-fold increase in spleen weight/body weight ratio

abnormal T cell subpopulation ratio ( J:91235 )

• an increase in the CD4+/CD8+ ratio

increased leukocyte cell number ( J:91235 )

• severe leukocytosis

increased immunoglobulin level ( J:91235 )

• hypergammaglobulinemia; immunoglobulin deposits are seen along the basal lamina and in the subjacent connective tissue

enlarged lymph nodes ( J:91235 )

• enlarged lymph nodes result in the swelling of the ventrolateral neck

autoimmune response ( J:91235 )

increased susceptibility to autoimmune disorder ( J:91235 )

• develop an autoimmune phenotype in late adulthood (after 6 months of age) exhibiting features of systemic lupus erythematosus

increased anti-single stranded DNA antibody level ( J:91235 )

• increase in levels of anti-ssDNA IgG antibody levels

chronic inflammation ( J:91235 )

• 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

increased inflammatory response ( J:91235 )

arteritis ( J:91235 )

• 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

increased incidence of corneal inflammation ( J:91235 )

• variable severity of keratitis: dense leukocyte infiltrates are concentrated in the outer half of the corneal stroma, which is thickened and vascularized

kidney inflammation ( J:91235 )

• 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

glomerulonephritis ( J:91235 )

skin inflammation ( J:91235 )

• 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

dermatitis ( J:91235 )

vision/eye

increased incidence of corneal inflammation ( J:91235 )

• variable severity of keratitis: dense leukocyte infiltrates are concentrated in the outer half of the corneal stroma, which is thickened and vascularized

abnormal cornea epithelium morphology ( J:91235 )

• sometimes the epithelium exhibits focal dysplasia characterized by an irregular thickening and a loss of its normal stratification

renal/urinary system

increased urine protein level ( J:91235 )

• low-level microproteinuria

hematuria ( J:91235 )

• low-level microhematuria

kidney inflammation ( J:91235 )

• 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

glomerulonephritis ( J:91235 )

cardiovascular system

arteritis ( J:91235 )

• 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

enlarged spleen ( J:91235 )

• 3-fold increase in spleen weight/body weight ratio

abnormal T cell subpopulation ratio ( J:91235 )

• an increase in the CD4+/CD8+ ratio

increased leukocyte cell number ( J:91235 )

• severe leukocytosis

increased immunoglobulin level ( J:91235 )

• hypergammaglobulinemia; immunoglobulin deposits are seen along the basal lamina and in the subjacent connective tissue

homeostasis/metabolism

increased urine protein level ( J:91235 )

• low-level microproteinuria

hematuria ( J:91235 )

• low-level microhematuria

integument

skin inflammation ( J:91235 )

• 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

dermatitis ( J:91235 )

abnormal epidermal layer morphology ( J:91235 )

• skin contains numerous intraepithelial keratin 'horn' cysts and a highly papillomatotic interface to the underlying corium

hyperkeratosis ( J:91235 )

epidermal hyperplasia ( J:91235 )

skin lesions ( J:91235 )

• 75% of mutants aged between 6 and 18 months of age develop wart-like protrusions and exulcerations of the skin

• skin lesions resemble human seborrheic keratosis

spontaneous skin ulceration ( J:91235 )

• 75% of mutants aged between 6 and 18 months of age develop exulcerations of the skin

abnormal skin condition ( J:91235 )

epidermal cyst ( J:91235 )

• skin develops numerous intraepithelial keratin 'horn' cysts in late adulthood (after 6 months of age)

growth/size/body

epidermal cyst ( J:91235 )

• skin develops numerous intraepithelial keratin 'horn' cysts in late adulthood (after 6 months of age)

enlarged spleen ( J:91235 )

• 3-fold increase in spleen weight/body weight ratio

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
seborrheic keratosis		DOID:6498	OMIM:182000	J:91235
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:91235

Genotype
MGI:3702892

cx3

• Allelic Composition: Psen1^tm1Bdes/Psen1^tm1Bdes; Psen2^tm1Bdes/Psen2^tm1Bdes
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

Psen1^tm1Bdes/Psen1^tm1Bdes Psen2^tm1Bdes/Psen2^tm1Bdes embryos display severe growth retardation at E9.5

mortality/aging

prenatal lethality, complete penetrance ( J:58118 )

• time of lethality is not specified although mutants are recovered at E9.5

growth/size/body

embryonic growth retardation ( J:58118 )

• embryos are developmentally retarded by about half a day at E9.5

embryo

abnormal vitelline vasculature morphology ( J:58118 )

• vasculogenesis of the yolk sac is delayed in most mutants

caudal body truncation ( J:58118 )

• embryos are posteriorly truncated

embryonic growth retardation ( J:58118 )

• embryos are developmentally retarded by about half a day at E9.5

kinked neural tube ( J:58118 )

• neural tube often has a kinked appearance

abnormal visceral yolk sac morphology ( J:58118 )

• yolk sacs do not expand properly and often have a blistered appearance

abnormal vitelline vascular remodeling ( J:58118 )

• although the initial vascular plexus and primitive red blood cells form, organization into a discrete network of vitelline vessels does not occur

cardiovascular system

abnormal vitelline vasculature morphology ( J:58118 )

• vasculogenesis of the yolk sac is delayed in most mutants

distended pericardium ( J:58118 )

• occasionally the pericardial sacs are enlarged

abnormal blood circulation ( J:58118 )

• embryo is devoid of blood circulation

nervous system

kinked neural tube ( J:58118 )

• neural tube often has a kinked appearance

abnormal brain development ( J:58118 )

• fusion of headfolds is delayed

abnormal forebrain development ( J:58118 )

• mutants at E9.5 have a vestigial forebrain

abnormal hindbrain development ( J:58118 )

• mutants at E9.5 have a vestigial hindbrain