Phenotypes associated with this allele

• Allele Symbol: Plau^tm1Mlg
• Allele Name: targeted mutation 1, Richard C Mulligan
• Allele ID: MGI:1857289
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Plau^tm1Mlg/Plau^tm1Mlg	B6.129S2-Plau^tm1Mlg	MGI:4836581
hm2	Plau^tm1Mlg/Plau^tm1Mlg	B6.Cg-Plau^tm1Mlg	MGI:3526528
hm3	Plau^tm1Mlg/Plau^tm1Mlg	either: B6.Cg-Plau^tm1Mlg or (involves: Black Swiss * C57BL/6)	MGI:3526393
hm4	Plau^tm1Mlg/Plau^tm1Mlg	involves: 129S2/SvPas * C57BL/6	MGI:2662716
cx5	Apoe^tm1Bres/Apoe^tm1Bres Plau^tm1Mlg/Plau^tm1Mlg	involves: 129 * C57BL/6	MGI:3527476
cx6	Plau^tm1Mlg/Plau^tm1Mlg Thbd^tm2Rdr/Thbd^tm2Rdr	involves: 129S2/SvPas	MGI:3844987
cx7	Plat^tm1Mlg/Plat^tm1Mlg Plau^tm1Mlg/Plau^tm1Mlg	involves: 129S2/SvPas * C57BL/6	MGI:3526176
cx8	Plau^tm1Mlg/Plau^tm1Mlg Tg(RIP1-Tag)2Dh/0	involves: C57BL/6	MGI:3527475

Genotype
MGI:4836581

hm1

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: B6.129S2-Plau^tm1Mlg

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

mortality/aging

premature death ( J:164542 )

• only 5 of 8 mice survive for a year

immune system

chronic inflammation ( J:164542 )

• chronic inflammation is secondary to fibrin deposition

increased inflammatory response ( J:164542 )

• in the liver and trachea

• however, leukocyte accumulation in standard models of inflammation is normal

liver inflammation ( J:164542 )

• the number of inflammatory foci is increased compared to in wild-type mice

trachea inflammation ( J:164542 )

• all mice exhibit inflammation in the trachea

liver/biliary system

decreased liver glycogen level ( J:164542 )

liver inflammation ( J:164542 )

• the number of inflammatory foci is increased compared to in wild-type mice

liver fibrosis ( J:164542 )

• 2.5-fold more frequent in number compared with Plau^tm1.1Bug or Plaur^tm1Jld homozygotes

homeostasis/metabolism

decreased liver glycogen level ( J:164542 )

abnormal response to injury ( J:164542 )

• following treatment with carbon tetrachloride, substantial areas of necrosis persist in the liver unlike in similarly treated wild-type mice

• however, skin wound healing is normal

respiratory system

trachea inflammation ( J:164542 )

• all mice exhibit inflammation in the trachea

abnormal trachea morphology ( J:164542 )

• all mice exhibit inflammation in the trachea with basement membrane hyperplasia and desquamation of the tracheal epithelium unlike in wild-type mice

trachea fibrosis ( J:164542 )

• mice exhibit fibrosis in the trachea unlike wild-type mice

adipose tissue

decreased total body fat amount ( J:164542 )

growth/size/body

cachexia ( J:164542 )

• some mice die before 1 year with a wasting syndrome

Genotype
MGI:3526528

hm2

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: B6.Cg-Plau^tm1Mlg

neoplasm

decreased metastatic potential ( 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

abnormal tumor morphology ( 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 ( 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

digestive/alimentary system

abnormal rectum morphology ( J:73613 )

• in males with rectal prolapse, the rectal mucosa is exteriorized and evaginated

rectal prolapse ( 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

abnormal perineum morphology ( J:73613 )

• in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa

endocrine/exocrine glands

herniated seminal vesicle ( 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

impaired macrophage chemotaxis ( 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

decreased T cell proliferation ( 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

abnormal acute phase protein level ( J:68083 )

• at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers

abnormal cytokine level ( 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

decreased susceptibility to induced arthritis ( 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

decreased inflammatory response ( 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

muscle

impaired skeletal muscle regeneration ( 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 ( 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

abnormal perineum morphology ( J:73613 )

• in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa

herniated seminal vesicle ( 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

decreased susceptibility to induced arthritis ( 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

abnormal acute phase protein level ( J:68083 )

• at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers

abnormal cytokine level ( 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

hematopoietic system

impaired macrophage chemotaxis ( 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

decreased T cell proliferation ( 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

cellular

impaired macrophage chemotaxis ( 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

decreased T cell proliferation ( 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

Genotype
MGI:3526393

hm3

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: either: B6.Cg-Plau^tm1Mlg or (involves: Black Swiss * C57BL/6)

homeostasis/metabolism

reduced thrombolysis ( 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

Genotype
MGI:2662716

hm4

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: involves: 129S2/SvPas * C57BL/6

integument

abnormal facial skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the eartag

mortality/aging

mortality/aging ( J:17427 )

N • homozygotes display a normal lifespan relative to wild-type mice

growth/size/body

growth/size/body region phenotype ( J:17427 )

N • at 5 weeks of age, homozygotes exhibit a normal body weight relative to wild-type mice

heart left ventricle hypertrophy ( 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

abnormal facial skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the eartag

cardiovascular system

decreased susceptibility to induced choroidal neovascularization ( 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

heart left ventricle hypertrophy ( 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

cardiac interstitial fibrosis ( 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 ( J:95236 )

• at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion

digestive/alimentary system

rectal prolapse ( J:17427 )

• at ~22 weeks of age, 9% of homozygotes display rectal prolapse of a non-infectious origin

hearing/vestibular/ear

abnormal outer ear skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the eartag

hematopoietic system

hematopoietic system phenotype ( J:17427 )

N • homozygotes exhibit normal spontaneous lysis of a 125I-fibrin-labeled pulmonary plasma clot relative to wild-type

increased lymphocyte cell number ( 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

abnormal neutrophil physiology ( J:75573 , J:91980 )

• 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 (J:75573)

• 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 (J:91980)

• 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 (J:91980)

• in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (J:91980)

impaired neutrophil phagocytosis ( 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 ( 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 macrophage physiology ( 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 chemotaxis ( 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

immune system

increased lymphocyte cell number ( 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

abnormal acute phase protein level ( J:63134 , J:82604 )

• bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis (J:63134)

• 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 (J:82604)

abnormal cell-mediated immunity ( J:87817 , J:95638 )

• homozygotes fail to generate a type 2 immune response following schistosomal antigen challenge (J:87817)

• 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 (J:87817)

• homozygotes fail to generate a type 1 immune response in the lung during pulmonary fungal infection with C. neoformans (J:95638)

• 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 (J:95638)

abnormal neutrophil physiology ( J:75573 , J:91980 )

• 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 (J:75573)

• 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 (J:91980)

• 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 (J:91980)

• in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (J:91980)

impaired neutrophil phagocytosis ( 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 ( 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 macrophage physiology ( 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 chemotaxis ( 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

increased susceptibility to fungal infection ( 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 ( 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

heart left ventricle hypertrophy ( 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

increased ventricle muscle contractility ( 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

reproductive system phenotype ( J:17427 )

N • homozygotes display normal litter size and frequency of litters relative to wild-type mice

respiratory system

pulmonary interstitial fibrosis ( 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

decreased susceptibility to induced choroidal neovascularization ( 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

abnormal eyelid morphology ( J:17427 )

• at ~26 weeks of age, 5% homozygotes display severe non-healing ulcerations at the eyelids

nervous system

nervous system phenotype ( J:55243 , J:104962 )

N • 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 (J:55243)

N • Abeta40 and 42 levels are not increased in mutant brains relative to controls (J:104962)

homeostasis/metabolism

abnormal circulating protein level ( 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 thrombosis ( 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

increased susceptibility to induced thrombosis ( J:17427 )

• 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)

abnormal acute phase protein level ( J:63134 , J:82604 )

• bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis (J:63134)

• 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 (J:82604)

craniofacial

abnormal facial skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the eartag

cellular

cardiac interstitial fibrosis ( 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

impaired macrophage chemotaxis ( 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

impaired neutrophil phagocytosis ( 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:104962

Genotype
MGI:3527476

cx5

• Allelic Composition: Apoe^tm1Bres/Apoe^tm1Bres; Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: involves: 129 * C57BL/6

cardiovascular system

decreased susceptibility to atherosclerosis ( J:44387 )

• at >15 weeks of age, double homozygotes fed an atherogenic diet show only minimal destruction of the atherosclerotic aorta wall relative to Apoe^tm1Bres mice

• in double mutants, the media remain largely intact with continuous elastic membranes and multiple smooth-muscle cell layers; no infiltrating macrophages are detected, except at the base of the intimal plaque

• double mutants show no atherosclerotic aneurysmal dilation or rupture whereas Apoe^tm1Bres mice exhibit a >50% dilation in the diameter of the abdominal aorta

aortic elastic tissue lesions ( J:44387 )

• at >15 weeks of age, double homozygotes fed an atherogenic diet display minimal fragmentation of the internal elastic membranes (EMs) in 10% of plaques; in contrast, Apoe^tm1Bres mice show fragmentation of EMs in 51% of plaques, and perforating transmedial ulceration in 21% of plaques

Genotype
MGI:3844987

cx6

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg; Thbd^tm2Rdr/Thbd^tm2Rdr
• Genetic Background: involves: 129S2/SvPas

mortality/aging

embryonic lethality ( J:47676 )

Genotype
MGI:3526176

cx7

• Allelic Composition: Plat^tm1Mlg/Plat^tm1Mlg; Plau^tm1Mlg/Plau^tm1Mlg
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:17427 )

• double homozygotes exhibit a reduced lifespan with 17% dying at ~17 weeks of age

• 9 out of 22 double homozygotes survive until the end of an observation period of 30-40 weeks; only 3 out of 10 double mutants survive until 40-50 weeks

integument

abnormal facial skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the ears around the eartag

cellular

cellular necrosis ( J:17427 )

• pre-terminal double mutants display intestinal adhesions and occasionally ischemic tissue necrosis (uterus and intestines), possibly due to thrombosis

digestive/alimentary system

rectal prolapse ( J:17427 )

• at 8-12 weeks of age, 37% of double homozygotes display rectal prolapse of a non-infectious origin

• in double mutants, rectal prolapse develops with variable penetrance and onset but appears significantly earlier and at a much higher incidence than in single mutant mice

growth/size/body

abnormal facial skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the ears around the eartag

decreased body size ( J:17427 )

• at ~17 weeks, 17% of double homozygotes appear runted prior to death

decreased body weight ( J:17427 )

• at 23 weeks, the body weight of double homozygotes is approximately 2/3 that of wild-type mice

cachexia ( J:17427 )

• at ~17 weeks, 17% of double homozygotes exhibit cachexia prior to death

postnatal growth retardation ( J:17427 )

• after 3 weeks of age, double homozygotes appear growth retarded relative to wild-type mice

hearing/vestibular/ear

abnormal outer ear skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the ears around the eartag

reproductive system

reduced fertility ( J:17427 )

• double homozygotes display a significant reduction in fertility possibly because of poor health or large fibrin deposition in the gonads

decreased litter size ( J:17427 )

• double homozygous breeding pairs produce slightly fewer offspring per litter than wild-type breeding pairs

respiratory system

respiratory distress ( J:17427 )

• at ~17 weeks, 17% of double homozygotes exhibit dyspnea prior to death

vision/eye

abnormal eyelid morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes exhibit extensive non-healing ulcerations at the eyelids

homeostasis/metabolism

reduced thrombolysis ( J:17427 )

• double homozygotes exhibit a severe reduction in the rate of spontaneous plasma clot lysis relative to wild-type or Plat^tm1Mlg mutant mice

• in double mutants, lysis of 125I-fibrin-labeled pulmonary plasma clots remains significantly lower for up to 48 hrs but is not significantly different after 72 hrs

abnormal thrombosis ( J:17427 )

• pre-terminal double mutants exhibit spontaneous fibrin deposits in the liver, intestines, gonads, lungs, in non-healing ulcerations of the skin, ears and prolapsed rectum, and occasionally in the kidneys

craniofacial

abnormal facial skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the face

abnormal outer ear skin morphology ( J:17427 )

• at 8-12 weeks of age, 5% of double homozygotes show extensive non-healing ulcerations at the ears around the eartag

Genotype
MGI:3527475

cx8

• Allelic Composition: Plau^tm1Mlg/Plau^tm1Mlg; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: C57BL/6

neoplasm

increased carcinoma incidence ( J:65019 )

• at 13.5 weeks (end stage), mice homozygous for Plau^tm1Mlg and hemizygous for Tg(RIP1-Tag)2Dh show no differences in the number of angiogenic islets or collective tumor growth relative to Tg(RIP1-Tag)2Dh hemizygotes

cardiovascular system

cardiovascular system phenotype ( J:65019 )

N • at 10.5 weeks of age, mice homozygous for Plau^tm1Mlg and hemizygous for Tg(RIP1-Tag)2Dh show no differences in the frequency of angiogenic switching among premalignant islets relative to RIP1-Tag2 hemizygotes