Phenotypes associated with this allele

• Allele Symbol: Psen1^tm1Bdes
• Allele Name: targeted mutation 1, Bart de Strooper
• Allele ID: MGI:2149116
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Psen1^tm1Bdes/Psen1^tm1Bdes	involves: 129P2/OlaHsd	MGI:2174990
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:2174990

hm1

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

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:71037 )

• die late in embryogenesis

growth/size/body

abnormal body wall morphology ( J:95663 )

• about one third of mutants develop midline defects of the body wall

omphalocele ( J:95663 )

• about one third of mutants exhibit umbilical hernias containing loops of small intestine, covered only by atrophic epithelium

fetal growth retardation ( J:71037 )

• severe growth retardation, particularly in the caudal region

limbs/digits/tail

short tail ( J:71037 )

cardiovascular system

abnormal brain vasculature morphology ( J:95663 )

• within the cerebral anlage, there is a reduction of the numbers of small-caliber vessels in the basal hemisphere as early as E14 and capillaries are only rarely encountered

intracerebral hemorrhage ( J:95663 )

craniofacial

abnormal sagittal suture morphology ( J:95663 )

• the posterior segment of the sagittal suture immediately anterior to the occipital bone has narrow clefts, through which brain and leptomeningeal tissue protrudes into the subcutaneous space

abnormal neurocranium morphology ( J:95663 )

• about one third of mutants develop midline defects of the cranial vault

nervous system

abnormal brain vasculature morphology ( J:95663 )

• within the cerebral anlage, there is a reduction of the numbers of small-caliber vessels in the basal hemisphere as early as E14 and capillaries are only rarely encountered

intracerebral hemorrhage ( J:95663 )

abnormal neuronal migration ( J:95663 )

• multifocal overmigration of cortical plate neurons beyond their normal positions into the subarachnoid space

abnormal cortical marginal zone morphology ( J:95663 )

• overall density of cells in the marginal zone is reduced during the period of cortical development between E13 and E18, after being initially normal at E13, most notably of the Cajal-Retzius cells

• the extracellular matrix of the marginal zone is altered, with chondroitin sulfate proteoglycan and reeling content reduced after E12

decreased Cajal-Retzius cell number ( J:95663 )

abnormal cerebral cortex morphology ( J:95663 )

• cortical dysplasia develops between E13 and E18, with mutants showing lissencephalic lesions and completely dissolved cortical plate

• the cortical anlage of E15 mutants exhibits numerous islands of ectopic neurons along the brain surface, as a result of overmigration of cortical-plate neurons into the marginal zone and subarachnoid space

abnormal meninges morphology ( J:95663 )

• fibrotic thickening of leptomeninges, with up to five layers of fiberblasts

• the meninges and their underlying basement membrane either form bulges ensheathing the overmigrated neural tissue or show gaps

skeleton

abnormal sagittal suture morphology ( J:95663 )

• the posterior segment of the sagittal suture immediately anterior to the occipital bone has narrow clefts, through which brain and leptomeningeal tissue protrudes into the subcutaneous space

abnormal neurocranium morphology ( J:95663 )

• about one third of mutants develop midline defects of the cranial vault

cellular

abnormal neuronal migration ( J:95663 )

• multifocal overmigration of cortical plate neurons beyond their normal positions into the subarachnoid space

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:71037

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 corneal 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