General Terms and Conditions

Related Disease (OMIM) Terms

Alzheimer Disease; AD

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Plau^tm1Mlg/Plau^tm1Mlg

        involves: 129S2/SvPas * C57BL/6

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:17427)
  • homozygotes display a normal lifespan relative to wild-type mice
• growth/size phenotype
• *normal* growth/size phenotype (MGI Ref ID J:17427)
  • at 5 weeks of age, homozygotes exhibit a normal body weight relative to wild-type mice
• cardiovascular system phenotype
• cardiac interstitial fibrosis (MGI Ref ID J:95236)
  • in response to pressure overload, homozygotes show only minimal signs of maladaptation (i.e. myolysis, fibrosis or increased intercapillary distance) relative to wild-type mice
• increased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion
• left ventricle hypertrophy (MGI Ref ID J:95236)
  • after transverse aortic banding (TAB), i.e. acute pressure overload, homozygotes remain significantly protected against LV hypertrophy for at least 7 weeks
  • homozygotes display only a 20% increase in LV/body ratio and only a 22% increase in LV cardiomyocyte size relative to wild-type (~35% and ~40%, respectively)
  • at 7 weeks after TAB, LV systolic dysfunction and dilatation are only marginally detectable without signs of pulmonary edema
• resistance to induced choroidal neovascularization (MGI Ref ID J:82604)
  • in response to laser-induced injury of the Bruch's membrane, homozygotes display almost complete absence of choroidal neovascularization (CNV) at the site of trauma; in contrast, wild-type mice show a robust neovascular reaction
  • resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels
• digestive/alimentary phenotype
• rectal prolapse (MGI Ref ID J:17427)
  • at ~22 weeks of age, 9% of homozygotes display rectal prolapse of a non-infectious origin
• hearing/vestibular/ear phenotype
• abnormal outer ear morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype (MGI Ref ID J:17427)
  • homozygotes exhibit normal spontaneous lysis of a 125I-fibrin-labeled pulmonary plasma clot relative to wild-type
• increased lymphocyte cell number (MGI Ref ID J:63134)
  • at day 7 post-treatment, the decline in macrophage counts coincides with an increase in the percentage of lymphocytes found in the lungs of bleomycin-treated mice
• immune system phenotype
• abnormal cell-mediated immunity (MGI Ref ID J:87817)
  • homozygotes fail to generate a type 2 immune response following schistosomal antigen challenge
  • in response to schistosomal egg antigen (SEA), homozygotes fail to develop a delayed-type hypersensitivity response to SEA, do not polarize Ig production to IgE, fail to produce high levels of IL-4, IL-5, or IL-13 and generate pulmonary granulomas that are deficient in eosinophils
  • homozygotes fail to generate a type 1 immune response in the lung during pulmonary fungal infection with C. neoformans
  • in response to C. neoformans infection, homozygotes show impaired T cell proliferation in regional lymph nodes and fail to produce high levels of T1 cytokines (IFN-gamma and IL-12) in the lung; instead, mutants exhibit increased levels of IL-5, a T2 cytokine
• abnormal macrophage physiology (MGI Ref ID J:17427)
  • in contrast to wild-type, homozygotes exhibit no plasminogen-dependent breakdown of 125I-fibrin-labeled matrix and of 3H-proline-labeled subendothelial breakdown by thioglycollate-activated macrohages; invasion of macrophages into the peritoneal cavity remains unaffected
• impaired macrophage recruitment (MGI Ref ID J:63134)
  • 5 days after bleomycin treatment, homozygotes display a peak in lung macrophage levels that coincides with the peak time observed in wild-type mice; however, their marcophage levels are significantly reduced relative to wild-type
  • 7 days after bleomycin treatment, mutant and wild-type mice show a similar decrease in the number and percentage of macrophages found in the lung
• abnormal neutrophil physiology (MGI Ref ID J:75573)
  • 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit an enhanced antibacterial host defense, with less pneumococci in their lungs and increased neutrophil influx in the bronchoalveolar lavage fluid but no reduction in mortality relative to wild-type
  • relative to wild-type, purified neutrophils from mutant mice exhibit a ~50% reduction in superoxide production in response to fMLP (a potent chemotaxin and activator of neutrophils) across the entire dose range tested; repletion with murine uPA completely reverses the defect in superoxide generation
  • in response to fMLP, mutant neutrophils exhibit reduced neutrophil exocytosis of azurophilic granules (as shown by reduced myeloperoxidase release); however, this defect is not corrected by repletion with extracellular uPA
  • in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils
• impaired neutrophil phagocytosis (MGI Ref ID J:91980)
  • in vitro, purified neutrophils from mutant mice exhibit a significant reduction in phagocytosis of E. coli at all time points; repletion with murine uPA substantially reverses the defect in neutrophil phagocytosis
• impaired granulocyte bactericidal activity (MGI Ref ID J:91980)
  • in vitro, purified neutrophils from mutant mice display significant defects in several aspects of the antibacterial neutrophil activation process that lead to E. coli killing and effective host defense
• abnormal fibrinogen physiology (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis
  • after laser-induced injury of the Bruch's membrane, homozygotes show massive accumulation of fibrinogen-fibrin both in the retinal vessels, and in the bottom of the laser-induced trauma
• increased lymphocyte cell number (MGI Ref ID J:63134)
  • at day 7 post-treatment, the decline in macrophage counts coincides with an increase in the percentage of lymphocytes found in the lungs of bleomycin-treated mice
• increased susceptibility to fungal infection (MGI Ref ID J:95637)
  • 21 days after inoculation with Cryptococcus neoformans, homozygotes contain significantly higher lung CFUs than wild-type mice
  • C. neoformans-infected mutants disseminate the fungal pathogen to their spleen; eventually 15 out of 19 mutants (versus 3/19 wild-type) die from fungal meningitis
• increased susceptibility to parasitic infection (MGI Ref ID J:87817)
  • when primed homozygotes are challenged with schistosomal egg antigen (SEA) they exhibit a severe immune defect in response to this T2-eliciting antigen
• muscle phenotype
• increased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:17427)
  • homozygotes display normal litter size and frequency of litters relative to wild-type mice
• respiratory system phenotype
• pulmonary interstitial fibrosis (MGI Ref ID J:63134)
  • 14 days after bleomycin treatment, homozygotes exhibit an increase in lung hydroxyproline (collagen) content that is comparable to that observed in bleomycin-treated wild-type mice
  • histological analysis 14 days after lung injury indicates extensive interstitial fibrosis in mutant mice relative to wild-type; however, no hemorrhage or extensive collagen deposition is observed
  • 62% of bleomycin-treated homozygotes die as early as ~7 days after treatment, possibly as a result of extensive fibrosis
• vision/eye phenotype
• abnormal eyelid morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% homozygotes display severe non-healing ulcerations at the eyelids
• resistance to induced choroidal neovascularization (MGI Ref ID J:82604)
  • in response to laser-induced injury of the Bruch's membrane, homozygotes display almost complete absence of choroidal neovascularization (CNV) at the site of trauma; in contrast, wild-type mice show a robust neovascular reaction
  • resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:55243)
  • homozygotes subjected to focal cerebral ischemia induced by persistent occlusion of the left middle cerebral artery produce an infarct with a size that is comparable to that produced in wild-type mice
• homeostasis/metabolism phenotype
• abnormal circulating protein level (MGI Ref ID J:104962)
  • 3-6 month-old mice have elevated levels of plasma amyloid beta 42 (Abeta42) and Abeta40; by 11 months of age, difference in levels between mutants and controls has increased significantly
• abnormal fibrinogen physiology (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis
  • after laser-induced injury of the Bruch's membrane, homozygotes show massive accumulation of fibrinogen-fibrin both in the retinal vessels, and in the bottom of the laser-induced trauma
• thrombosis (MGI Ref ID J:17427)
  • homozygotes occasionally exhibit small, focal fibrin deposits in the intestines and in the sinusoids of the liver and extensive fibrin deposits in the ulcerated skin, ear or prolapsed rectum
  • in response to injection of pro-inflammatory endotoxin in the footpad, homozygotes exhibit overt venous thrombosis at a significantly higher incidence (90% versus 54%) and to a much larger extent than wild-type mice (60% of mutants show >4 thrombosed veins per tissue section versus only 15% in wild-type)
• craniofacial phenotype
• abnormal outer ear morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face
• other phenotype
• *normal* other phenotype (MGI Ref ID J:104962)
  • Abeta40 and 42 levels are not increased in mutant brains relative to controls

Plau^tm1Mlg/Plau^tm1Mlg

        either: B6.Cg-Plau^tm1Mlg or (involves: Black Swiss * C57BL/6)

• homeostasis/metabolism phenotype
• reduced thrombolysis (MGI Ref ID J:64220)
  • in a model of pulmonary microembolism, wild-type mice are able to clear 125I-microemboli rapidly with complete lysis by 5 hours; in contrast, mutants remain unable to lyse pulmonary microemboli throughout the 5-hr experimental period
  • in these mutants, impaired fibrinolysis can be rescued completely by providing urokinase exogenously

Plau^tm1Mlg/Plau^tm1Mlg

        B6.Cg-Plau^tm1Mlg

• tumorigenesis
• altered tumor morphology (MGI Ref ID J:65383)
  • 3 weeks after implantation of T241 fibrosarcoma cells, primary tumors from mutant mice appear to be better delineated and less hemorrhagic than tumors from wild-type mice
  • also, tumors from mutant mice show an increase in collagen deposition at the periphery of the lesion, forming a fibrous and thick pseudocapsule that is almost undetectable in tumors from wild-type mice
  • ultrastructurally, fibrosarcoma tumor neovessels formed in mutant mice are larger and less mature than tumor vessels from wild-type mice
• decreased tumor growth/size (MGI Ref ID J:65383)
  • 3 weeks after implantation of T241 fibrosarcoma cells, primary tumors from mutant mice are significantly smaller than tumors from wild-type mice
  • consistent with tumor growth suppression, tumor tissues from mutant mice exhibit lower proliferative and higher apoptotic indices relative to tumor tissues from wild-type mice
• decreased metastatic potential (MGI Ref ID J:65383)
  • following implantation of T241 fibrosarcoma cells, only a limited number of mutants develop metastatic lesions in the lung and brain; in contrast, almost all of wild-type mice display metastases to the same locations
  • notably, only mutants that survive for longer periods (2 months) after the injection develop these lesions, indicating a delay in metastasis
• digestive/alimentary phenotype
• abnormal perineum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa
• abnormal rectum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the rectal mucosa is exteriorized and evaginated
• rectal prolapse (MGI Ref ID J:73613)
  • starting at 6 months, male (but not female) homozygotes show a high incidence of rectal prolapse
  • in mutant males, rectal prolapse is irreducible and completely exteriorized by 12 months
• endocrine/exocrine gland phenotype
• herniated seminal glands (MGI Ref ID J:73613)
  • males with rectal prolapse develop an irreducible hernia of the seminal vesicles through the pelvic outlet and through a hiatus found between the iliococcygeus (ISC), the bulbocavrnosus (BC), and the tail
  • this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles
• immune system phenotype
• abnormal cytokine level (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:68083)
  • at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers
• decreased T cell proliferation (MGI Ref ID J:75303)
  • despite a normal antibody response to type II collagen, T cells from arthritic homozygotes show a reduced proliferative response and produce less interferon-gamma on antigen stimulation in vitro
• decreased inflammatory response (MGI Ref ID J:68083)
  • in response to glycerol-induced muscle degeneration, homozygotes display significantly reduced numbers of macrophages and neutrophils at the site of injury relative to wild-type
• impaired macrophage recruitment (MGI Ref ID J:68083)
  • in response to skeletal muscle degeneration, homozygotes display a 50% reduction in macrophage recruitment at the injury site 48 hours after glycerol-induced injury
• resistance to induced arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction
  • in this chronic systemic model, the affected limbs of mutants are rigid but not swollen; arthritis is largely confined to the ankle joint, with most joints in the feet appearing normal
  • surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type
• muscle phenotype
• abnormal muscle regeneration (MGI Ref ID J:68083)
  • in response to glycerol-induced injury, homozygotes exhibit a severe skeletal muscle regeneration defect relative to wild-type; this defect is apparent at 5 days but is most striking at 9 and 20 days after injury
  • at 5 days after injury, skeletal muscles from mutant mice appear edematous; in contrast to wild-type, no uninucleated, small myofibers are yet formed
  • at 7 days after injury, most injured skeletal muscles appear necrotic and show extensive fibrosis
  • at 9 and 20 days, numerous degenerated myotubes and fibrosis are still visible in mutant muscles whereas no signs of previous damage are detectable in wild-type muscles
  • systemic fibrinogen depletion via ancrod administration restores muscle regeneration: 9 days after injury, ancrod-treated mutants exhibit improved muscle regeneration, with centrally located nuclei inside the regenerated fibers
• myopathy (MGI Ref ID J:73613)
  • males with rectal prolapse, exhibit myopathic damage in the affected pelvic floor muscles (ISC, BC and LA)
  • most affected myofibers have centrally located nuclei; some show basophilic degeneration in the absence of denervation, fibrosis or inflammation
• reproductive system phenotype
• abnormal perineum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa
• herniated seminal glands (MGI Ref ID J:73613)
  • males with rectal prolapse develop an irreducible hernia of the seminal vesicles through the pelvic outlet and through a hiatus found between the iliococcygeus (ISC), the bulbocavrnosus (BC), and the tail
  • this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles
• skeleton phenotype
• resistance to induced arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction
  • in this chronic systemic model, the affected limbs of mutants are rigid but not swollen; arthritis is largely confined to the ankle joint, with most joints in the feet appearing normal
  • surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type
• homeostasis/metabolism phenotype
• abnormal cytokine level (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:68083)
  • at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers
• hematopoietic system phenotype
• decreased T cell proliferation (MGI Ref ID J:75303)
  • despite a normal antibody response to type II collagen, T cells from arthritic homozygotes show a reduced proliferative response and produce less interferon-gamma on antigen stimulation in vitro