Phenotypes Associated with This Genotype

Genotype
MGI:3815114

• Allelic Composition: Ccl2^tm1Rol/Ccl2^tm1Rol
• Genetic Background: B6.129S4-Ccl2^tm1Rol

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

Ccl2^tm1Rol/Ccl2^tm1Rol mice with experimental autoimmune encephalomyelitis show fewer inflammatory infiltrates in the spinal cord

immune system

abnormal macrophage chemotaxis ( J:109290 )

• the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice

• the total number of macrophages recruited is normal

impaired macrophage chemotaxis ( J:68145 , J:118606 , J:151874 )

• mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE (J:68145)

• initially following femoral artery excision (J:118606)

• only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls (J:151874)

increased neutrophil cell number ( J:118606 )

• 1 and 3 days after femoral artery excision, mice exhibit an earlier increase in neutrophil accumulation (measured by MPO activity) than in similarly treated wild-type mice

increased CD4-positive, alpha-beta T cell number ( J:68145 )

• in an EAE model, mutants show an increase in proportion of CD4+ cells and reduction in CD11b+CD4- in the CNS leukocyte infiltrates compared to wild-type, although total numbers of T cells are not different

increased osteoclast cell number ( J:109290 )

• at P5 during tooth eruption

• peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

decreased leukocyte cell number ( J:68145 )

• numbers of leukocytes isolated from CNS tissue during EAE attacks are about 1/3 of those from wild type mice with comparable EAE severity

decreased macrophage cell number ( J:147328 )

• age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

abnormal neutrophil physiology ( J:151874 )

• the number of neutrophils recruited to the peritoneum in an induced peritonitis model is almost double that controls

increased IgG level ( J:147328 )

• at 16 months, IgG is present in the retinal pigmented epithelium or choroids unlike in wild-type mice

• IgG light chain deposition in the retinal pigmented epithelium accumulates with age unlike in wild-type mice

increased IgG1 level ( J:68145 )

• significantly higher levels of anti-MOG35-55 IgG1 antibodies are seen in mutants compared to wild-type

abnormal chemokine level ( J:118606 , J:151874 )

• 1 day after femoral artery excision, muscles accumulate more chemoattractants (KC and MIP-2) than in similarly treated wild-type mice (J:118606)

• in thioglycollate- or zymosan- induced peritonitis models, no Ccl2 is detected while reduce levels of Ccl7 are present in peritoneal fluid (J:151874)

abnormal cytokine secretion ( J:68145 )

• MOG35-55-specific Th1 cytokine responses are diminished in mutants

abnormal chemokine secretion ( J:151874 )

• there is no Ccl2 (MCP-1) secretion by peritoneal macrophages activated in vitro compared to controls

• secretion of Ccl7 (MCP-3) and Ccl12 (MCP-5) is also dramatically reduced by these activated macrophages

decreased interferon-gamma secretion ( J:68145 )

• mutants exhibit reduced production of IFN-gamma in response to MOG35-55 induced EAE

increased interleukin-10 secretion ( J:68145 )

• mutants exhibit enhanced secretion of IL-10 in response to MOG35-55 induced EAE

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:68145 )

• homozygotes are resistant to active experimental autoimmune encephalomyelitis (EAE) induction with MOG35-55, with delayed onset of disease, reduced inflammatory reaction including impaired recruitment of macrophages to the central nervous system (CNS), and faster and complete recovery

• adoptive transfer of primed T cells from wild-type mice to naive homozygous mutant recipients does not mediate clinical EAE, however wild-type mice receiving mutant T cells do develop clinical EAE

vision/eye

retina photoreceptor degeneration ( J:147328 )

• at 16 months

abnormal retina pigment epithelium morphology ( J:147328 )

• after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice

• at 16 months, mice exhibit attenuation of the retinal pigmented epithelium unlike in wild-type mice

retina outer nuclear layer degeneration ( J:147328 )

• at 16 months

increased susceptibility to age-related retinal degeneration ( J:147328 )

• at 16 months, mice exhibit progressive outer retinal degeneration and confluent areas of visible atrophy unlike in wild-type mice

• at 18 months, mice exhibit geographic atrophy unlike in wild-type mice

retina deposits ( J:147328 )

• after 9 months of age, mice exhibit subretinal deposits similar to drusen that increase with age unlike in wild-type mice

abnormal optic choroid morphology ( J:147328 )

• age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

abnormal choriocapillaris morphology ( J:147328 )

• at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice

choroidal neovascularization ( J:147328 )

• at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice

• after 18 months, 4 of 15 mice exhibit choroidal neovascularization with angiographic leakage unlike in wild-type mice

• between 18 and 27 months, neovasculatization breaches the Bruch membrane and causes retinal pigmented epithelium and photoreceptor disruptions unlike in wild-type mice

abnormal Bruch membrane morphology ( J:147328 )

• the Bruch membrane is thickened compared to in wild-type mice after 9 months of age

• at 20 months, the outer Bruch membrane is breached by choriocapillary processes unlike in wild-type mice

behavior/neurological

alcohol aversion ( J:102583 )

♀ • in female mice

alcohol preference ( J:102583 )

• male mice exhibit a greater ethanol preference compared with wild-type (in post hoc analysis) mice, Ccr2^tm1Mae homozygotes, and Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes

• female mice exhibit a greater ethanol preference compared with Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes and Ccr2^tm1Mae homozygotes

decreased alcohol consumption ( J:102583 )

♀ • in female mice compared with wild-type mice and Ccr2^tm1Mae homozygotes

abnormal conditioned taste aversion behavior ( J:102583 )

• mice exhibit a stronger response to ethanol in an ethanol-induced conditioned taste aversion test compared with similarly treated wild-type mice

• however, saccharin consumption is normal

increased fluid intake ( J:102583 )

• mice exhibit increased drinking of an ethanol solution compared with Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes and Ccr2^tm1Mae homozygotes

• mice exhibit increased drinking of a quinine solution compared with wild-type mice

increased alcohol consumption ( J:102583 )

• male mice consume more ethanol than wild-type (in post hoc analysis) mice and Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes

• female mice consume more ethanol than Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes

impaired righting response ( J:102583 )

• mice exhibit longer duration of ethanol-induced loss of righting response compared with similarly treated wild-type mice

cardiovascular system

abnormal choriocapillaris morphology ( J:147328 )

• at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice

choroidal neovascularization ( J:147328 )

• at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice

• after 18 months, 4 of 15 mice exhibit choroidal neovascularization with angiographic leakage unlike in wild-type mice

• between 18 and 27 months, neovasculatization breaches the Bruch membrane and causes retinal pigmented epithelium and photoreceptor disruptions unlike in wild-type mice

abnormal blood circulation ( J:118606 )

• following femoral artery excision, mice exhibit a delay in the restoration of perfusion compared with similarly treated wild-type mice

nervous system

retina photoreceptor degeneration ( J:147328 )

• at 16 months

pigmentation

abnormal retina pigment epithelium morphology ( J:147328 )

• after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice

• at 16 months, mice exhibit attenuation of the retinal pigmented epithelium unlike in wild-type mice

lipofuscinosis ( J:147328 )

• after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice

hematopoietic system

abnormal macrophage chemotaxis ( J:109290 )

• the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice

• the total number of macrophages recruited is normal

impaired macrophage chemotaxis ( J:68145 , J:118606 , J:151874 )

• mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE (J:68145)

• initially following femoral artery excision (J:118606)

• only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls (J:151874)

increased neutrophil cell number ( J:118606 )

• 1 and 3 days after femoral artery excision, mice exhibit an earlier increase in neutrophil accumulation (measured by MPO activity) than in similarly treated wild-type mice

increased CD4-positive, alpha-beta T cell number ( J:68145 )

• in an EAE model, mutants show an increase in proportion of CD4+ cells and reduction in CD11b+CD4- in the CNS leukocyte infiltrates compared to wild-type, although total numbers of T cells are not different

increased osteoclast cell number ( J:109290 )

• at P5 during tooth eruption

• peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

decreased leukocyte cell number ( J:68145 )

• numbers of leukocytes isolated from CNS tissue during EAE attacks are about 1/3 of those from wild type mice with comparable EAE severity

decreased macrophage cell number ( J:147328 )

• age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

abnormal neutrophil physiology ( J:151874 )

• the number of neutrophils recruited to the peritoneum in an induced peritonitis model is almost double that controls

increased IgG level ( J:147328 )

• at 16 months, IgG is present in the retinal pigmented epithelium or choroids unlike in wild-type mice

• IgG light chain deposition in the retinal pigmented epithelium accumulates with age unlike in wild-type mice

increased IgG1 level ( J:68145 )

• significantly higher levels of anti-MOG35-55 IgG1 antibodies are seen in mutants compared to wild-type

homeostasis/metabolism

abnormal chemokine level ( J:118606 , J:151874 )

• 1 day after femoral artery excision, muscles accumulate more chemoattractants (KC and MIP-2) than in similarly treated wild-type mice (J:118606)

• in thioglycollate- or zymosan- induced peritonitis models, no Ccl2 is detected while reduce levels of Ccl7 are present in peritoneal fluid (J:151874)

decreased physiological sensitivity to xenobiotic ( J:110695 )

• bleomycin-treated mice fail to exhibit skin fibrosis with normal collagen fibrils and few infiltrating macrophages and neutrophils unlike similarly treated wild-type mice

abnormal response to injury ( J:118606 )

• following femoral artery excision, mice exhibit a delay in the restoration of perfusion, extended period of increased ischemic muscle weight at day 1 and 7, earlier increase in neutrophil accumulation (measured by MPO activity) at day 1 and 3, increased chemoattractants (KC and MIP-2) levels at day 1, decreased accumulation of inflammatory infiltrate at day 3, delayed macrophage recruitment, large regions of necrotic muscle, increased adipocyte accumulation in the muscle, and impaired muscle regeneration compared with similarly treated wild-type mice

craniofacial

premature tooth eruption ( J:109290 )

• tooth eruption begins at P14 instead of P16 as in wild-type mice

• from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice

skeleton

premature tooth eruption ( J:109290 )

• tooth eruption begins at P14 instead of P16 as in wild-type mice

• from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice

increased osteoclast cell number ( J:109290 )

• at P5 during tooth eruption

• peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

muscle

increased muscle weight ( J:118606 )

• after 1 and 7 days, mice subjected to femoral artery excision exhibit an extended period of increased ischemic muscle weight compared with similarly treated wild-type mice

abnormal skeletal muscle morphology ( J:118606 )

• following femoral artery excision, muscles accumulate more adipocytes than in similarly treated wild-type mice

skeletal muscle necrosis ( J:118606 )

• following femoral artery excision

impaired skeletal muscle regeneration ( J:118606 )

• muscle regeneration, as measured by LDH and fiber size, is impaired following femoral artery excision

cellular

abnormal macrophage chemotaxis ( J:109290 )

• the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice

• the total number of macrophages recruited is normal

impaired macrophage chemotaxis ( J:68145 , J:118606 , J:151874 )

• mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE (J:68145)

• initially following femoral artery excision (J:118606)

• only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls (J:151874)

growth/size/body

premature tooth eruption ( J:109290 )

• tooth eruption begins at P14 instead of P16 as in wild-type mice

• from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration		DOID:10871	OMIM:PS603075	J:147328