Mouse Genome Informatics
hm1
    Psen1tm1Bdes/Psen1tm1Bdes
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

growth/size/body
• about one third of mutants develop midline defects of the body wall
• about one third of mutants exhibit umbilical hernias containing loops of small intestine, covered only by atrophic epithelium
• severe growth retardation, particularly in the caudal region

limbs/digits/tail

cardiovascular system
• 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

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

nervous system
• 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
• multifocal overmigration of cortical plate neurons beyond their normal positions into the subarachnoid space
• 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
• 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
• 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
• 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
• about one third of mutants develop midline defects of the cranial vault

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

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:71037


Mouse Genome Informatics
cx2
    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
• 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
• 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 Genome Informatics
cx3
    Psen1tm1Bdes/Psen1tm1Bdes
Psen2tm1Bdes/Psen2tm1Bdes

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Psen1tm1Bdes/Psen1tm1Bdes Psen2tm1Bdes/Psen2tm1Bdes embryos display severe growth retardation at E9.5

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

growth/size/body
• embryos are developmentally retarded by about half a day at E9.5

embryogenesis
• vasculogenesis of the yolk sac is delayed in most mutants
• although the initial vascular plexus and primitive red blood cells form, organization into a discrete network of vitelline vessels does not occur
• embryos are posteriorly truncated
• neural tube often has a kinked appearance
• yolk sacs do not expand properly and often have a blistered appearance
• embryos are developmentally retarded by about half a day at E9.5

cardiovascular system
• vasculogenesis of the yolk sac is delayed in most mutants
• although the initial vascular plexus and primitive red blood cells form, organization into a discrete network of vitelline vessels does not occur
• occasionally the pericardial sacs are enlarged
• embryo is devoid of blood circulation

nervous system
• neural tube often has a kinked appearance
• fusion of headfolds is delayed
• mutants at E9.5 have a vestigial forebrain
• mutants at E9.5 have a vestigial hindbrain