Mouse Genome Informatics
hm1
    Mmp9tm1Tvu/Mmp9tm1Tvu
129S6/SvEvTac-Mmp9tm1Tvu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice exhibit a normal local Shwartman response namely thrombohemorrhagic vasculitis (J:113463)


Mouse Genome Informatics
hm2
    Mmp9tm1Tvu/Mmp9tm1Tvu
B6.129S6-Mmp9tm1Tvu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• injected A549 cells exhibit an increase in early apoptosis compared to in wild-type mice
• mice injected with Lewis lung carcinoma or A549 cells exhibit a decrease in tumors compared with similarly treated wild-type mice


Mouse Genome Informatics
hm3
    Mmp9tm1Tvu/Mmp9tm1Tvu
C3N.129S6-Mmp9tm1Tvu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in B. burgdorferi-infected mice compared with similarly treated wild-type mice
• B. burgdorferi-infected mice exhibit reduced arthritis compared with similarly treated wild-type mice
• however, spirochete numbers in the joint are normal
• mice infected with Borrelia burgdorferi exhibit less ankle swelling, joint inflammation, and arthritis than similarly treated wild-type mice
• however, mice exhibit normal development of carditis when infected with B. burgdorferi

skeleton
• in B. burgdorferi-infected mice compared with similarly treated wild-type mice
• B. burgdorferi-infected mice exhibit reduced arthritis compared with similarly treated wild-type mice
• however, spirochete numbers in the joint are normal
• in B. burgdorferi-infected mice compared with similarly treated wild-type mice


Mouse Genome Informatics
hm4
    Mmp9tm1Tvu/Mmp9tm1Tvu
either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• hypertrophic cartilage zone in the metatarsals is about twice that of wild-type at birth and becomes more pronounced with growth so that by 3 weeks, it is 6-8 times as long
• abnormal growth plate development, however after 3 weeks of age, aberrant apoptosis, vascularization, and ossification compensate to remodel the enlarged growth plate and ultimately produce an axial skeleton of normal appearance except for the shorter long bones
• ectopic areas of ossification begin to appear within the hypertrophic zone at 4 weeks of age
• apoptosis of hypertrophic chondrocytes is delayed
• by 3 weeks of age, when the hypertrophic zone is lengthened, aberrant apoptosis begins in the middle of the hypertrophic cartilage and is seen around the areas of ossification throughout the hypertrophic zone at 4 weeks
• exhibit lengthened zone of hypertrophic cartilage with no difference in the reserve or proliferating zones
• long bones are about 10% shorter than in wild-type
• area of metaphyseal trabecular bone is shorter
• ectopic areas of ossification begin to appear within the hypertrophic zone at 4 weeks of age and the ectopic ossification proceeds rapidly so that in some bones the entire zone of hypertrophic cartilage is ossified, leading to a large area of trabecular bone, however this is resolved with subsequent remodeling so that by 8 weeks, bones appear normal
• secondary (epiphyseal) ossification sites are delayed until 2.5 weeks of age, however, by 3 weeks of age, these sites are completely ossified as in wild-type

limbs/digits/tail
• hypertrophic cartilage zone in the metatarsals is about twice that of wild-type at birth and becomes more pronounced with growth so that by 3 weeks, it is 6-8 times as long


Mouse Genome Informatics
hm5
    Mmp9tm1Tvu/Mmp9tm1Tvu
either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit reduced angiogenic response to peripheral leg ischemia; do not observe an increase in capillary density and see reduced capillary perfusion capacity and fewer points of capillary intersections (decreased branching) after ischemia


Mouse Genome Informatics
hm6
    Mmp9tm1Tvu/Mmp9tm1Tvu
either: FVB.129S6-Mmp9tm1Tvu or (involves: 129S6/SvEvTac)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit less left ventricular dilation after experimental myocardial infarction and show less collagen accumulation in the infracted area than seen in wild-type

homeostasis/metabolism
• exhibit less left ventricular dilation after experimental myocardial infarction and show less collagen accumulation in the infracted area than seen in wild-type


Mouse Genome Informatics
hm7
    Mmp9tm1Tvu/Mmp9tm1Tvu
FVB.129S6-Mmp9tm1Tvu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• DSS-treated mice exhibit no mortality unlike similarly treated wild-type mice
• however, mice exhibit normal mortality in response to Salmonella typhimurium-induced systemic sepsis

cardiovascular system
• exhibit increased neovascularization post myocardial infarction, as shown by increased total vessel density and normalized vessel distribution between subendo- and epicardial regions relative to wild-type after coronary artery ligation
• exhibit an increased angiogenic potential after myocardial infarction, as shown by the presence of newly formed vessels in the infarct region
• exhibit higher end-systolic pressure and dP/dtmax than wild-type after myocardial infarction, despite similar infarct sizes
• exhibit an increased infarct-to-septal wall thickness ratio, attenuated wall thinning, improved left ventricular function, and reduced peak macrophage infiltration into the infarct zone relative to wild-type after myocardial infarction

immune system
• DSS-treated mice exhibit no weight loss, mortality or lymphocyte accumulation in the colon, reduced neutrophil accumulation, colon shortening, intestinal inflammation, and intestinal injury, and fewer incidence of diarrhea and bleeding compared with similarly treated wild-type mice
• mice treated orally with Salmonella typhimurium to induce colitis exhibit reduced weight loss and destruction of crypt architecture compared with similarly treated wild-type mice
• neutrophil chemotatic response to fMLP is greater than for wild-type cells
• polymononuclear cell migration through Matri-gel-coated membrane in response to fMLP is greater compared with similarly treated wild-type cells

homeostasis/metabolism
• exhibit an increased infarct-to-septal wall thickness ratio, attenuated wall thinning, improved left ventricular function, and reduced peak macrophage infiltration into the infarct zone relative to wild-type after myocardial infarction
• DSS-treated mice exhibit no mortality unlike similarly treated wild-type mice
• however, mice exhibit normal mortality in response to Salmonella typhimurium-induced systemic sepsis

muscle
• exhibit higher end-systolic pressure and dP/dtmax than wild-type after myocardial infarction, despite similar infarct sizes

digestive/alimentary system
• DSS-treated mice exhibit no weight loss, mortality or lymphocyte accumulation in the colon, reduced neutrophil accumulation, colon shortening, intestinal inflammation, and intestinal injury, and fewer incidence of diarrhea and bleeding compared with similarly treated wild-type mice
• mice treated orally with Salmonella typhimurium to induce colitis exhibit reduced weight loss and destruction of crypt architecture compared with similarly treated wild-type mice

hematopoietic system
• neutrophil chemotatic response to fMLP is greater than for wild-type cells
• polymononuclear cell migration through Matri-gel-coated membrane in response to fMLP is greater compared with similarly treated wild-type cells


Mouse Genome Informatics
hm8
    Mmp9tm1Tvu/Mmp9tm1Tvu
FVB.Cg-Mmp9tm1Tvu/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice infected with West Nile virus exhibit decreased mortality compared with similarly treated wild-type mice
• however, mice exhibit a normal survival when injected intracerebrally with West Nile virus

immune system
• mice infected with West Nile virus exhibit decreased mortality, brain viral load, CD45+ leukocyte infiltration into brain tissue, and blood brain barrier permeability compared with similarly treated wild-type mice
• however, mice exhibit a normal response to West Nile virus infection when injected intracerebrally with the virus
• mice infected with West Nile virus exhibit decreased mortality compared with similarly treated wild-type mice
• however, mice exhibit a normal survival when injected intracerebrally with West Nile virus

digestive/alimentary system
• mice exhibit an increased in the number of intestinal goblet cells compared to in wild-type mice
• however, the number of goblet cells per crypt is normal

behavior/neurological
• 3 days after spinal nerve ligation, mice exhibit less spontaneous pain and early phase mechanical allodynia compared with similarly treated wild-type mice
• however, mice exhibit normal neuropathic pain by 10 days following spinal nerve ligation

homeostasis/metabolism
• mice treated with tumor necrosis factor-related weak inducer of apoptosis (TWEAK or Tnfsf12) exhibit increased body and muscle weight, intact basement membrane, and reduced myopathy, clustering of inflammatory cells, and number of necrotic fibers in the muscle compared with similarly treated wild-type mice
• 3 days after spinal nerve ligation, mice exhibit less spontaneous pain and early phase mechanical allodynia compared with similarly treated wild-type mice (J:133660)
• however, mice exhibit normal neuropathic pain by 10 days following spinal nerve ligation (J:133660)
• following hepatic ischemia and reperfusion, hepatic apoptosis is decreased compared to in similarly treated wild-type mice (J:148923)

cardiovascular system
• mice infected with West Nile virus exhibit decreased blood brain barrier permeability compared with similarly treated wild-type mice

nervous system
• mice infected with West Nile virus exhibit decreased blood brain barrier permeability compared with similarly treated wild-type mice

growth/size
• in tumor necrosis factor-related weak inducer of apoptosis (TWEAK or Tnfsf12)-treated mice compared with similarly treated wild-type mice

muscle
• the weight of the tibialis anterior in mice treated with Tnfsf12-treated mice is greater than in similarly treated wild-type mice

integument
• 3 days after spinal nerve ligation, mice exhibit less spontaneous pain and early phase mechanical allodynia compared with similarly treated wild-type mice
• however, mice exhibit normal neuropathic pain by 10 days following spinal nerve ligation


Mouse Genome Informatics
hm9
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129/Sv * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• DNFB-sensitized and challenged mice have lower IL10 levels compared with similarly treated wild-type mice despite normal capacity of spleen cells to produce IL10 after LPS exposure

immune system
• DNFB-sensitized and challenged mice have lower IL10 levels compared with similarly treated wild-type mice despite normal capacity of spleen cells to produce IL10 after LPS exposure
• DNFB-sensitized and challenged mice exhibit a prolonged response and delayed resolution of inflammation compared with similarly treated wild-type mice
• however, resolution of phenol elicited inflammation is normal


Mouse Genome Informatics
hm10
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• CVB3-infected mice exhibit increased morbidity compared with similarly treated wild-type mice

homeostasis/metabolism
• in CVB3-infected mice compared to in similarly treated wild-type mice
• exhibit attenuated arterial remodeling in response to vascular injury (ligation of carotid artery) compared to wild-type, with decreases in late lumen loss, neointimal thickening, and migration of smooth muscle cells into the neointima and an accumulation of interstitial collagen
• in CVB3-infected mice compared to in similarly treated wild-type mice
• in CVB3-infected mice compared to in similarly treated wild-type mice
• ovalbumin sensitized and exposed mice exhibit reduced CCL17 protein levels in the bronchoalveolar lavage fluid compared with similarly treated wild-type mice
• mice sensitized and exposed to ovalbumin fail to exhibit the airway inflammation observed in similarly treated wild-type mice
• mice sensitized and exposed to ovalbumin exhibit impaired ovalbumin-IgE production compared with similarly treated wild-type mice
• following ovalbumin treatment, the numbers of dendritic cell in the bronchoalveolar lavage fluid and airway walls does not increase as much as in similarly treated wild-type mice
• ovalbumin sensitized and exposed mice exhibit reduced CCL17 protein levels in the bronchoalveolar lavage fluid compared with similarly treated wild-type mice
• following induction of aortic aneurysm with elastase, mice develop fewer aneurysms with less of an increase in aortic diameter compared with similarly treated wild-type mice (J:62760)
• however, mice reconstituted with wild-type bone marrow exhibit normal susceptibility to elastase-induced aortic aneurysms (J:62760)
• mice are resistant to traumatic brain injury compared with similarly treated wild-type mice with smaller traumatic lesion volumes (J:79422)
• mice are resistant to the pathogenic activity of anti-mBP180 (Col17a1) antibodies that induce subepidermal blistering in wild-type mice (J:91478)
• however, mice reconstituted with wild-type neutrophils exhibit normal response to anti-Col17a1 antibodies (J:91478)
• following IgG-induction of acute lung injury, mice exhibit reduced lung injury, decreased BALF protein leakage, and perivascular edema compared with similarly treated wild-type mice (J:114188)
• however, the number of macrophages and neutrophils recruited to the lungs is normal in mice with IgG-induced acute lung injury (J:114188)

immune system
• CVB3-infected mice exhibit an increase in T cell infiltration in the heart compared with similarly treated wild-type mice
• following ovalbumin treatment, the numbers of dendritic cell in the bronchoalveolar lavage fluid and airway walls does not increase as much as in similarly treated wild-type mice
• mice sensitized and exposed to ovalbumin exhibit impaired ovalbumin-IgE production compared with similarly treated wild-type mice
• in CVB3-infected mice compared to in similarly treated wild-type mice
• in CVB3-infected mice compared to in similarly treated wild-type mice
• ovalbumin sensitized and exposed mice exhibit reduced CCL17 protein levels in the bronchoalveolar lavage fluid compared with similarly treated wild-type mice
• in vitro, chemotaxis of dendritic cells in response to CCL5 (RANTES) and CCL20 (MIP-3alpha) is impaired compared with similarly treated wild-type cells
• however, homing of dendritic cells from airways to lymph nodes in mice is normal
• migration of Langerhans cells is impaired compared to in wild-type mice
• however, maturation of Langerhans cells is normal
• mice sensitized and exposed to ovalbumin fail to exhibit the airway inflammation observed in similarly treated wild-type mice
• Coxsackievirus B3 (CVB3)-infected mice exhibit increased morbidity, viral load, serum IFN-gamma and IFN-beta, left ventricular posterior wall and interventricular septum thickness, and cardiac injury as determined by increased myocytolysis, calcification, and cellular infiltrate and decreased ejection fraction and E wave compared with similarly treated wild-type mice
• CVB3-infected mice exhibit increased morbidity compared with similarly treated wild-type mice

cardiovascular system
• following induction of aortic aneurysm with elastase, mice develop fewer aneurysms with less of an increase in aortic diameter compared with similarly treated wild-type mice
• however, mice reconstituted with wild-type bone marrow exhibit normal susceptibility to elastase-induced aortic aneurysms
• mice exhibit 45% less ischemia-induced retinal neovascularization compared with similarly treated wild-type mice
• CVB3-infected mice exhibit increased interventricular septum thickness compared with similarly treated wild-type mice
• CVB3-infected mice exhibit increased left ventricular posterior wall thickness compared with similarly treated wild-type mice
• in CVB3-infected mice compared to in similarly treated wild-type mice
• in CVB3-infected mice compared to in similarly treated wild-type mice
• isolated aortic smooth muscle cells show decreased migration and capacity to contract collagen in vitro
• exhibit attenuated arterial remodeling in response to vascular injury (ligation of carotid artery) compared to wild-type, with decreases in late lumen loss, neointimal thickening, and migration of smooth muscle cells into the neointima and an accumulation of interstitial collagen
• on day 9 post-infection in CVB3-infected mice compared to in similarly treated wild-type mice
• on days 3 and 9, CVB3-infected mice exhibit decreased E wave compared with similarly treated wild-type mice
• myocytolysis is increased in CVB3-infected mice compared to in similarly treated wild-type mice
• CVB3-infected mice exhibit an increase in T cell infiltration in the heart compared with similarly treated wild-type mice

nervous system
• exhibit a decrease in the number of mature oligondendrocytes at P10, however no differences in oligodendrocyte precursor cell numbers
• exhibit decreased myelination in the corpus callosum at P7 and P10, but not at P14, as evidenced by decreased MBP expression

muscle
• isolated aortic smooth muscle cells show decreased migration and capacity to contract collagen in vitro
• on day 9 post-infection in CVB3-infected mice compared to in similarly treated wild-type mice

hematopoietic system
• following ovalbumin treatment, the numbers of dendritic cell in the bronchoalveolar lavage fluid and airway walls does not increase as much as in similarly treated wild-type mice
• mice sensitized and exposed to ovalbumin exhibit impaired ovalbumin-IgE production compared with similarly treated wild-type mice

vision/eye
• mice exhibit 45% less ischemia-induced retinal neovascularization compared with similarly treated wild-type mice


Mouse Genome Informatics
hm11
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• on days 24 and 30, ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue eosinophil numbers compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue lymphocyte numbers compared with similarly treated wild-type mice
• on day 24, ovalbumin-treated mice exhibit an increased in Th2 helper cells in the bronchoalveolar lavage compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue macrophage cell numbers compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue monocyte numbers compared with similarly treated wild-type mice
• on day 24 hours in ovalbumin-treated wild-type mice compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased ovalbumin-IgE compared with similarly treated wild-type mice
• on day 24, alum treated mice exhibit an increase in CCL22 in lung tissue compared with similarly treated wild-type mice
• on days 24 and 30, ovalbumin-treated mice exhibit increased CCL11 in the bronchoalveolar lavage compared with similarly treated wild-type mice
• on day 24, ovalbumin-treated mice exhibit an increase in bronchoalveolar lavage CCL22 compared with similarly treated wild-type mice
• on day 30, ovalbumin-treated mice exhibit an increase in lung tissue CCL22 compared with similarly treated wild-type mice
• however, mice exhibit normal levels of CCL2, CCL3, and CCL5 following ovalbumin treatment
• ovalbumin-treated mice exhibit decreased IFN-gamma in bronchoalveolar lavage compared with similarly treated wild-type mice
• on day 24, T cells from alum-treated mice exhibit increased IFN-gamma secretion compared with cells from similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased IL13 in bronchoalveolar lavage and lung tissue compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased IL4 in bronchoalveolar lavage and lung tissue compared with similarly treated wild-type mice
• on day 24, T cells from ovalbumin-treated mice exhibit increased IL4 secretion compared with cells from similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased IL5 in lung tissue compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased lung inflammation with increased total cells, eosinophils, macrophages, lymphocytes, and monocytes in bronchoalveolar lavage and lung tissue compared with similarly treated wild-type mice
• mice infected with Streptoccocus pneumoniae to in the right forebrain exhibit higher blood and spleen bacterial titers compared with similarly treated wild-type mice
• in experimental peritonitis, mice exhibit higher spleen bacterial titers compared with similarly treated wild-type mice

homeostasis/metabolism
• on day 24, alum treated mice exhibit an increase in CCL22 in lung tissue compared with similarly treated wild-type mice
• on days 24 and 30, ovalbumin-treated mice exhibit increased CCL11 in the bronchoalveolar lavage compared with similarly treated wild-type mice
• on day 24, ovalbumin-treated mice exhibit an increase in bronchoalveolar lavage CCL22 compared with similarly treated wild-type mice
• on day 30, ovalbumin-treated mice exhibit an increase in lung tissue CCL22 compared with similarly treated wild-type mice
• however, mice exhibit normal levels of CCL2, CCL3, and CCL5 following ovalbumin treatment

respiratory system
• ovalbumin-treated mice exhibit increased lung inflammation with increased total cells, eosinophils, macrophages, lymphocytes, and monocytes in bronchoalveolar lavage and lung tissue compared with similarly treated wild-type mice

hematopoietic system
• on days 24 and 30, ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue eosinophil numbers compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue lymphocyte numbers compared with similarly treated wild-type mice
• on day 24, ovalbumin-treated mice exhibit an increased in Th2 helper cells in the bronchoalveolar lavage compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue macrophage cell numbers compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit an increase in the bronchoalveolar lavage and lung tissue monocyte numbers compared with similarly treated wild-type mice
• on day 24 hours in ovalbumin-treated wild-type mice compared with similarly treated wild-type mice
• ovalbumin-treated mice exhibit increased ovalbumin-IgE compared with similarly treated wild-type mice


Mouse Genome Informatics
hm12
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• when tested at 24 hours, mice exhibit reduced memory in hippocampus-dependent context conditioning compared with similarly treated wild-type mice
• however, mice tested at 30 hours for cued conditioning is normal

nervous system
• long term potentiation is smaller in magnitude and shorter in duration than in wild-type mice
• however, mice exhibit normal NMDA receptor-dependent long term depression and paired pulse facilitation


Mouse Genome Informatics
hm13
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit significantly reduced carotid artery intimal hyperplasia in response to vascular injury and fewer intimal smooth muscle cells
• exhibit impairment of smooth muscle cell migration through a gelatin-coated membrane towards a chemoattractant and in a wound assay4
• isolated smooth muscle cells exhibit impaired ability to compact collagen gels, to assemble fibrillar collagen from exogenous monomers, and to attach to gelatin

muscle
• exhibit impairment of smooth muscle cell migration through a gelatin-coated membrane towards a chemoattractant and in a wound assay4
• isolated smooth muscle cells exhibit impaired ability to compact collagen gels, to assemble fibrillar collagen from exogenous monomers, and to attach to gelatin


Mouse Genome Informatics
hm14
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following myelodepletion with 5-fluorouracil (5-FU), 72% of mice die unlike similarly treated wild-type mice

hematopoietic system
• restoration of myeloid and megakaryotic lineages in 5-FU-treated mice is impaired compared to in similarly treated wild-type mice
• restoration of myeloid and megakaryotic lineages in 5-FU-treated mice is impaired compared to in similarly treated wild-type mice
• following myelodepletion with 5-fluorouracil (5-FU), mice exhibit delayed recovery compared with similarly treated wild-type mice
• following myelodepletion with 5-fluorouracil (5-FU), fewer hematopoietic stem cells enter S phase compared to in similarly treated wild-type mice
• in transplantation experiments, chemokine-induced mobilization of bone marrow repopulating cells is impaired compared to in similarly treated wild-type mice
• mobilization of bone-marrow derived circulating endothelial cell progenitors is impaired compared to in similarly treated wild-type mice

homeostasis/metabolism
• following myelodepletion with 5-fluorouracil (5-FU), 72% of mice die unlike similarly treated wild-type mice
• following optic nerve ligation, retinas fail to exhibit apoptosis unlike in similarly treated wild-type mice
• 24 hours following cerebral ischemia, mice exhibit reduced ischemic lesion volumes compared with similarly treated wild-type mice
• however, mice subjected to cerebral ischemia exhibit normal neurological deficits

nervous system
• 24 hours following cerebral ischemia, mice exhibit reduced ischemic lesion volumes compared with similarly treated wild-type mice
• however, mice subjected to cerebral ischemia exhibit normal neurological deficits

immune system
• restoration of myeloid and megakaryotic lineages in 5-FU-treated mice is impaired compared to in similarly treated wild-type mice

vision/eye
• following optic nerve ligation, retinas fail to exhibit apoptosis unlike in similarly treated wild-type mice

cellular
• following optic nerve ligation, retinas fail to exhibit apoptosis unlike in similarly treated wild-type mice
• restoration of myeloid and megakaryotic lineages in 5-FU-treated mice is impaired compared to in similarly treated wild-type mice


Mouse Genome Informatics
hm15
    Mmp9tm1Tvu/Mmp9tm1Tvu
involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• wild-type neurons co-cultured with microglial cells exposed to TFN-alpha exhibit decreased cell death compared to neurons co-cultured with similarly treated wild-type microglial cells

homeostasis/metabolism
• at days 3, 5, and 7, mice exhibit delayed wound compared with similarly treated wild-type mice

cellular
• wild-type neurons co-cultured with microglial cells exposed to TFN-alpha exhibit decreased cell death compared to neurons co-cultured with similarly treated wild-type microglial cells


Mouse Genome Informatics
cx16
    Dmdmdx/Dmdmdx
Mmp9tm1Tvu/Mmp9tm1Tvu

B10.Cg-Mmp9tm1Tvu Dmdmdx
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• mice exhibit improved muscle and sarcolemmal structure, more uniform fiber diameter, reduced inflammatory cell between adjacent fibers, and decreased necrosis and fibrosis compared with Dmdmdx homozygotes (J:150030)
• myofiber regeneration is increased compared to in Dmdmdx homozygotes (J:150030)

immune system
• fewer macrophages accumulate in the muscles compared to in Dmdmdx homozygotes (J:150030)

hematopoietic system
• fewer macrophages accumulate in the muscles compared to in Dmdmdx homozygotes (J:150030)


Mouse Genome Informatics
cx17
    Dmdmdx/Dmdmdx
Mmp9tm1Tvu/Mmp9+

B10.Cg-Mmp9tm1Tvu Dmdmdx
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• mice exhibit improved muscle and sarcolemmal structure, more uniform fiber diameter, reduced inflammatory cell between adjacent fibers, and decreased necrosis and fibrosis compared with Dmdmdx homozygotes (J:150030)
• mice exhibit higher muscle force production compared with Dmdmdx homozygotes (J:150030)
• myofiber regeneration is increased compared to in Dmdmdx homozygotes (J:150030)

immune system
• fewer macrophages accumulate in the muscles compared to in Dmdmdx homozygotes (J:150030)

hematopoietic system
• fewer macrophages accumulate in the muscles compared to in Dmdmdx homozygotes (J:150030)


Mouse Genome Informatics
cx18
    Mmp9tm1Tvu/Mmp9tm1Tvu
Rag2tm1Fwa/Rag2tm1Fwa

B6.129S-Rag2tm1Fwa Mmp9tm1Tvu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice injected with A549 cells exhibit a reduction in the number of tumors that develop compared with similarly treated wild-type mice
• however, A549 cell tumor growth is normal


Mouse Genome Informatics
cx19
    Mmp2tm1Ito/Mmp2tm1Ito
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• following laser trauma, mice exhibit decreased choroidal neovascularization compared with similarly treated single homozygote

vision/eye
• following laser trauma, mice exhibit decreased choroidal neovascularization compared with similarly treated single homozygote


Mouse Genome Informatics
cx20
    Apoetm1Unc/Apoetm1Unc
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• following temporary ligation, mice develop intimal atherosclerotic plaques with reduced volume, length, smooth muscle cells, and intraplaque foam cells and macrophages compared with similarly treated Apoetm1Unc homozygotes
• following temporary ligation, fewer smooth muscle cells are found in atherosclerotic plaques compared to in similarly treated Apoetm1Unc homozygotes

immune system
• following temporary ligation, fewer foam cells and macrophages are found in atherosclerotic plaques compared to in similarly treated Apoetm1Unc homozygotes

muscle
• following temporary ligation, fewer smooth muscle cells are found in atherosclerotic plaques compared to in similarly treated Apoetm1Unc homozygotes

hematopoietic system
• following temporary ligation, fewer foam cells and macrophages are found in atherosclerotic plaques compared to in similarly treated Apoetm1Unc homozygotes


Mouse Genome Informatics
cx21
    Mmp9tm1Tvu/Mmp9tm1Tvu
Sftpdtm1Jhf/Sftpdtm1Jhf

involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• as in Sftpdtm1Jhf, mice exhibit enlarged alveolar spaces compared with wild-type mice with foamy macrophage and lymphocyte infiltrates


Mouse Genome Informatics
cx22
    Mmp9tm1Tvu/Mmp9tm1Tvu
Rag2tm1Fwa/Rag2tm1Fwa

involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mice injected with tumor cells exhibit reduced lung tumor burden compared with similarly treated wild-type mice with reduced tumor size
• metastatic lung tumors in mice injected with tumors cells exhibit decreased staining for blood vessels compared with equivalent tumors in wild-type mice
• metastatic lung tumors in mice injected with tumors cells exhibit decreased size compared with tumors induced in similarly treated wild-type mice


Mouse Genome Informatics
cx23
    Col4a3tm1Jhm/Col4a3tm1Jhm
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• double homozygotes exhibit no differences in the progression of glomerulonephritis compared with single Col4a3tm1Jhm mutants, suggesting that MMP9 does not play a major role in the progression of Alport syndrome

renal/urinary system
• double homozygotes exhibit no differences in the progression of glomerulonephritis compared with single Col4a3tm1Jhm mutants, suggesting that MMP9 does not play a major role in the progression of Alport syndrome
• at 8 weeks, double homozygotes exhibit the characteristic splitting and thickening of the glomerular basement membrane observed in the Col4a3tm1Jhm mouse model of Alport syndrome
• thickening of the glomerular basement membrane observed at 8 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Alport Syndrome, Autosomal Recessive 203780 J:63137


Mouse Genome Informatics
cx24
    Hspg2tm1Ref/Hspg2tm1Ref
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• short and thick
• severely disorganized

limbs/digits/tail
• short and thick


Mouse Genome Informatics
cx25
    Mmp13tm1.1Werb/Mmp13tm1.1Werb
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S2/SvPas * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size

skeleton
• the front of ossification is similar to that seen in Mmp9 single homozygotes
• the normal columnar architecture is lost
• seen in the long bones, more severe than in either single homozygote
• development of the bone marrow cavity is delayed
• decreased trabecular bone formation and abnormal growth plate development result in dramatically shortened skeletal elements
• development of the secondary site of ossification is delayed


Mouse Genome Informatics
cx26
    Mmp9tm1Tvu/Mmp9tm1Tvu
Timp1tm1Pds/Timp1tm1Pds

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• double mutants are as susceptible to corneal bacterial infection as wild-type mice unlike Timp1 single homozygotes which show decreased susceptibility (J:94836)


Mouse Genome Informatics
cx27
    Mmp12tm1Sds/Mmp12tm1Sds
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• exhibit a decrease in the number of mature oligondendrocytes at P10, however no differences in oligodendrocyte precursor cell numbers
• exhibit a similar decrease in myelination in the corpus callosum at P7 and P10, but not at P14, as single homozygous mutants

cardiovascular system
• following induction of aortic aneurysm with elastase, mice develop fewer aneurysms with less of an increase in aortic diameter compared with similarly treated wild-type mice

homeostasis/metabolism
• following induction of aortic aneurysm with elastase, mice develop fewer aneurysms with less of an increase in aortic diameter compared with similarly treated wild-type mice


Mouse Genome Informatics
cx28
    Mmp8tm1Otin/Mmp8tm1Otin
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice exhibit a normal local Shwartman response namely thrombohemorrhagic vasculitis (J:113463)


Mouse Genome Informatics
cx29
    Mmp9tm1Tvu/Mmp9tm1Tvu
Tg(SOD1*G93A)1Gur/0

involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice survive 31% longer than Tg(SOD1*G93A)1Gur mice (J:141587)

nervous system
N
• neuron loss observed in Tg(SOD1*G93A)1Gur mice is attenuated (J:141587)

immune system
• TNF-alpha staining is absent from neuronal cells in the spinal cord unlike in Tg(SOD1*G93A)1Gur mice


Mouse Genome Informatics
cx30
    Mmp9tm1Tvu/Mmp9tm1Tvu
Tg(KRT14-HPV16)wt1Dh/0

involves: 129S6/SvEvTac * C57BL/6 * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 27% of mice develop squamous cell carcinomas (SCCs) in the epidermis with more malignancy (increased aggressiveness and higher grade) compared to in Tg(KRT14-HPV16)wt1Dh mice
• mice exhibit fewer incidence of malignant conversions compared with Tg(KRT14-HPV16)wt1Dh mice
• 27% of mice develop squamous cell carcinomas (SCCs) in the epidermis compared to 50% of Tg(KRT14-HPV16)wt1Dh mice
• however, the numbers of SCCs per mouse is the same as in Tg(KRT14-HPV16)wt1Dh mice, and expression of the wild-type allele restores normal Tg(KRT14-HPV16)wt1Dh-induced neoplasia

integument
• compared to in Tg(KRT14-HPV16)wt1Dh mice
• at 2 months, all mice exhibit mild hyperplastic epidermis compared to in wild-type mice but not as severe as in Tg(KRT14-HPV16)wt1Dh mice
• at 4 months, 20% of mice develop epidermal dysplasia unlike in wild-type mice
• at 7 months, 90% of mice exhibit epidermal dysplasia unlike in wild-type mice
• 27% of mice develop squamous cell carcinomas (SCCs) in the epidermis with more malignancy (increased aggressiveness and higher grade) compared to in Tg(KRT14-HPV16)wt1Dh mice

cellular
• compared to in Tg(KRT14-HPV16)wt1Dh mice


Mouse Genome Informatics
cx31
    Mmp9tm1Tvu/Mmp9tm1Tvu
Tg(MMTV-PyVT)634Mul/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Background Sensitivity: mice exhibit reduced lung metastasis compared with Tg(MMTV-PyVT)634Mul mice unlike on a background lacking C57BL/6 with an 80% reduction in surface tumor number, a 76% reduction in total tumor area, and a slight reduction in average tumor size
• metastatic lung tumors exhibit decreased staining for blood vessels compared with equivalent tumors in Tg(MMTV-PyVT)634Mul mice
• proliferation and apoptosis rates of metastatic tumor cells are decreased compared with cells from Tg(MMTV-PyVT)634Mul mice with the balance resulting in reduced tumor size
• development of mammary gland tumors is similar to in Tg(MMTV-PyVT)634Mul mice


Mouse Genome Informatics
cx32
    Mmp13tm1Jdar/Mmp13tm1Jdar
Mmp9tm1Tvu/Mmp9tm1Tvu

involves: 129S6/SvEvTac * C57BL/6J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• at days 3, 5, and 7, mice exhibit delayed wound closure with decreased vascular density at the wound compared with similarly treated wild-type mice
• during wound healing, mice exhibit reduced wound contraction and myofibroblast formation compared with similarly treated wild-type mice
• however, vascular density at the wound recovers by day 14

cellular
• in unstimulated or TGF-beta1-stimulated dermal fibroblasts compared with similarly treated wild-type fibroblasts

skeleton

growth/size

cardiovascular system
• vascular density is decreased at healing wounds compared to in similarly treated wild-type mice


Mouse Genome Informatics
cx33
    Mmp9tm1Tvu/Mmp9tm1Tvu
Tg(MMTV-PyVT)634Mul/0

involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Background Sensitivity: development of mammary gland tumors and metastasis are similar to in Tg(MMTV-PyVT)634Mul mice unlike on a background containing C57BL/6