Phenotypes associated with this allele

• Allele Symbol: Cx3cr1^tm1Litt
• Allele Name: targeted mutation 1, Dan R Littman
• Allele ID: MGI:2670351
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	B6.129P2(Cg)-Cx3cr1^tm1Litt/J	MGI:4834191
hm2	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	B6.129P2-Cx3cr1^tm1Litt	MGI:4833984
hm3	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	C.129P2-Cx3cr1^tm1Litt	MGI:2670353
hm4	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	involves: 129P2/OlaHsd	MGI:4833981
hm5	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	involves: 129P2/OlaHsd * C57BL/6	MGI:2670352
ht6	Cx3cr1^tm1Litt/Cx3cr1^+	B6.129P2-Cx3cr1^tm1Litt	MGI:4833985
cx7	Cd1d1^tm1Luc/Cd1d1^tm1Luc Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	B6.129-Cd1d1^tm1Luc Cx3cr1^tm1Litt	MGI:4834138
cx8	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4834196
cx9	Cx3cr1^tm1Litt/Cx3cr1^+ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4834197
cx10	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt H2-Ab1^b-tm1Hpl/H2-Ab1^+	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:4833982
cx11	Ccl2^tm1Rol/Ccl2^tm1Rol Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J	MGI:5527432
cx12	Ccr2^tm2.1Ifc/Ccr2^tm2.1Ifc Cx3cr1^tm1Litt/Cx3cr1^+	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:4868437
cx13	Ccr2^tm2.1Ifc/Ccr2^tm2.1Ifc Cx3cr1^tm1Litt/Cx3cr1^tm1Litt	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:4868438
cx14	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Tg(SOD1*G93A)1Gur/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4833986

Genotype
MGI:4834191

hm1

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: B6.129P2(Cg)-Cx3cr1^tm1Litt/J

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:139390 )

N • mice exhibit normal response (dopamine nerve loss, increased body temperature, and microgliosis) to methamphetamine treatment

Genotype
MGI:4833984

hm2

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: B6.129P2-Cx3cr1^tm1Litt

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis

vision/eye

abnormal ocular fundus morphology ( J:265696 )

• mice show numerous white/yellow fundus lesions at 16 months of age but not at 3 months

abnormal retina photoreceptor morphology ( J:265696 )

• marker analysis indicates that photoreceptor maturation is abnormal with impaired outer segment elongation

abnormal photoreceptor connecting cilium morphology ( J:265696 )

• overall cilium structure is unaffected, however cilium proteins show altered distribution in the transitional zone during photoreceptor maturation

decreased retina cone cell number ( J:265696 )

• cone number is reduced from P30 in the periphery and in the central retina at P90

• however, outer nuclear layer thickness is not altered in either the peripheral or central retina

short photoreceptor outer segment ( J:265696 )

• mice show shortened outer segments in P21 retina

retina cone cell degeneration ( J:265696 )

• from P30 on

abnormal retina outer nuclear layer morphology ( J:265696 )

• microglial processes are often seen extending deep into the outer nuclear layer where photoreceptors reside

retina outer nuclear layer degeneration ( J:265696 )

• cell loss is seen in the outer nuclear layer of 16 month old retina but not 3 month old retina

retina degeneration ( J:265696 )

• late-stage retinal degeneration

retina gliosis ( J:265696 )

• retina shows increased Muller cell gliosis from around eye opening at P14, becoming significant from 1 month of age, and extensive gliosis, particularly within the inner plexiform layer at 3 months of age

decreased a-wave amplitude ( J:265696 )

• 22% decrease in amplitude of the a-wave at P270 but not earlier, indicating a late onset of reduced rod-related function

decreased b-wave amplitude ( J:265696 )

• cone-related function is reduced from P17, shows no increase in response coincident with photoreceptor maturation, the functional deficit remains at P30 and P90, while no difference is seen at P270, with a decrease in b wave amplitude at P17, P30, and P90

nervous system

brainstem hemorrhage ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis

increased neuron apoptosis ( J:110266 )

• following LPS exposure, neuron apoptosis is increased unlike in heterozygous mice

• LPS-induced neurotoxicity is cell-autonomous

• however, mice subjected to adoptive transfer experiments and treated with an IL1 receptor antagonist exhibit reduced neuron apoptosis

• however, adoptive transfer into Il1r null mice abolishes neuron apoptosis

increased susceptibility to dopaminergic neuron neurotoxicity ( J:110266 )

• mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit more severe neurotoxicity than similarly treated wild-type mice

abnormal microglial cell morphology ( J:265696 )

• increase in microglia numbers in the outer nuclear layer from P14 and a trend for increased microglial process number from P14 becoming significant at P90

• presence of microglial processes in the outer retinal is increased at P14 compared with P90, with levels further increased at P270

• microglia at the level of the photoreceptor terminals exhibit normal soma size and process number with increased process length, indicating that microglia are not classically activated

microgliosis ( J:110266 )

• intense and widespread following LPS exposure

abnormal microglial cell physiology ( J:110266 , J:265696 )

• migration of microglial cells in LPS-treated mice is impaired unlike in similarly treated heterozygous mice (J:110266)

• however, adoptive transfer into Il1r null mice restores microglial cell migration (J:110266)

• microglial-cone interactions are increased in the central and peripheral retina at P21 (J:265696)

brain inflammation ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis

abnormal retina photoreceptor morphology ( J:265696 )

• marker analysis indicates that photoreceptor maturation is abnormal with impaired outer segment elongation

abnormal photoreceptor connecting cilium morphology ( J:265696 )

• overall cilium structure is unaffected, however cilium proteins show altered distribution in the transitional zone during photoreceptor maturation

decreased retina cone cell number ( J:265696 )

• cone number is reduced from P30 in the periphery and in the central retina at P90

• however, outer nuclear layer thickness is not altered in either the peripheral or central retina

short photoreceptor outer segment ( J:265696 )

• mice show shortened outer segments in P21 retina

retina cone cell degeneration ( J:265696 )

• from P30 on

demyelination ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, mice exhibit more severe demyelination compared with similarly treated wild-type mice

immune system

immune system phenotype ( J:129712 )

N • mice exhibit normal response to murine cytomegalovirus infection

decreased NK cell number ( J:129712 )

• in the central nervous system following induction of experimental autoimmune encephalomyelitis

abnormal microglial cell morphology ( J:265696 )

• increase in microglia numbers in the outer nuclear layer from P14 and a trend for increased microglial process number from P14 becoming significant at P90

• presence of microglial processes in the outer retinal is increased at P14 compared with P90, with levels further increased at P270

• microglia at the level of the photoreceptor terminals exhibit normal soma size and process number with increased process length, indicating that microglia are not classically activated

microgliosis ( J:110266 )

• intense and widespread following LPS exposure

abnormal leukocyte physiology ( J:124722 )

• following arterial injury, monocyte recruitment is impaired compared to in similarly treated wild-type mice

abnormal NK cell physiology ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, recruitment of NK cells is impaired compared to in similarly treated wild-type mice

abnormal microglial cell physiology ( J:110266 , J:265696 )

• migration of microglial cells in LPS-treated mice is impaired unlike in similarly treated heterozygous mice (J:110266)

• however, adoptive transfer into Il1r null mice restores microglial cell migration (J:110266)

• microglial-cone interactions are increased in the central and peripheral retina at P21 (J:265696)

increased susceptibility to experimental autoimmune encephalomyelitis ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, mice exhibit earlier onset, higher mortality, and more severe EAE symptoms (nonremitting spastic paralysis, increased hemorrhagic inflammation, and extensive demyelination) compared with similarly treated wild-type mice

• following induction of experimental autoimmune encephalomyelitis, recruitment of NK cells is impaired compared to in similarly treated wild-type mice

• however, priming of encephalitogenic T cells and NKT cell numbers are normal

brain inflammation ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis

cardiovascular system

brainstem hemorrhage ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis

decreased vascular smooth muscle cell proliferation ( J:124722 )

• following arterial injury, vascular smooth muscle cell proliferation is decreased compared to in similarly treated wild-type mice

• in vitro, vascular smooth muscle cells fail to proliferate in response to CXCL1 unlike similarly treated wild-type cells

abnormal vascular wound healing ( J:124722 )

• following arterial injury, mice exhibit decreased intimal hyperplasia, impaired monocyte recruitment into the vascular wall, and decreased vascular smooth muscle cell proliferation compared to in similarly treated wild-type mice

• however, mice exhibit normal luminal and medial areas and platelet function

homeostasis/metabolism

abnormal vascular wound healing ( J:124722 )

• following arterial injury, mice exhibit decreased intimal hyperplasia, impaired monocyte recruitment into the vascular wall, and decreased vascular smooth muscle cell proliferation compared to in similarly treated wild-type mice

• however, mice exhibit normal luminal and medial areas and platelet function

increased susceptibility to dopaminergic neuron neurotoxicity ( J:110266 )

• mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit more severe neurotoxicity than similarly treated wild-type mice

behavior/neurological

paralysis ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, mice exhibit nonremitting spastic paralysis

hematopoietic system

decreased NK cell number ( J:129712 )

• in the central nervous system following induction of experimental autoimmune encephalomyelitis

abnormal microglial cell morphology ( J:265696 )

• increase in microglia numbers in the outer nuclear layer from P14 and a trend for increased microglial process number from P14 becoming significant at P90

• presence of microglial processes in the outer retinal is increased at P14 compared with P90, with levels further increased at P270

• microglia at the level of the photoreceptor terminals exhibit normal soma size and process number with increased process length, indicating that microglia are not classically activated

microgliosis ( J:110266 )

• intense and widespread following LPS exposure

abnormal leukocyte physiology ( J:124722 )

• following arterial injury, monocyte recruitment is impaired compared to in similarly treated wild-type mice

abnormal NK cell physiology ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, recruitment of NK cells is impaired compared to in similarly treated wild-type mice

abnormal microglial cell physiology ( J:110266 , J:265696 )

• migration of microglial cells in LPS-treated mice is impaired unlike in similarly treated heterozygous mice (J:110266)

• however, adoptive transfer into Il1r null mice restores microglial cell migration (J:110266)

• microglial-cone interactions are increased in the central and peripheral retina at P21 (J:265696)

muscle

decreased vascular smooth muscle cell proliferation ( J:124722 )

• following arterial injury, vascular smooth muscle cell proliferation is decreased compared to in similarly treated wild-type mice

• in vitro, vascular smooth muscle cells fail to proliferate in response to CXCL1 unlike similarly treated wild-type cells

cellular

decreased vascular smooth muscle cell proliferation ( J:124722 )

• following arterial injury, vascular smooth muscle cell proliferation is decreased compared to in similarly treated wild-type mice

• in vitro, vascular smooth muscle cells fail to proliferate in response to CXCL1 unlike similarly treated wild-type cells

abnormal photoreceptor connecting cilium morphology ( J:265696 )

• overall cilium structure is unaffected, however cilium proteins show altered distribution in the transitional zone during photoreceptor maturation

increased neuron apoptosis ( J:110266 )

• following LPS exposure, neuron apoptosis is increased unlike in heterozygous mice

• LPS-induced neurotoxicity is cell-autonomous

• however, mice subjected to adoptive transfer experiments and treated with an IL1 receptor antagonist exhibit reduced neuron apoptosis

• however, adoptive transfer into Il1r null mice abolishes neuron apoptosis

increased susceptibility to dopaminergic neuron neurotoxicity ( J:110266 )

• mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit more severe neurotoxicity than similarly treated wild-type mice

Genotype
MGI:2670353

hm3

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: C.129P2-Cx3cr1^tm1Litt

immune system

immune system phenotype ( J:84544 )

N • normal monocyte extravasation and subsequent differentiation into macrophages in response to intraperitoneal injection of thioglycolate, a model of acute peritonitis

Genotype
MGI:4833981

hm4

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:95694 )

• S. typhimurium-infected mice exhibit a higher organ bacterial load and die within 6 days of infection unlike similarly treated heterozygous and wild-type mice

immune system

increased dendritic cell number ( J:210086 )

• antibiotic-treated mice exhibit increased numbers of all subsets of dendritic cells in the mesenteric lymph nodes as compared to untreated controls

• mice treated with antibiotic and infected with non-invasive Salmonella exhibit increased numbers of only CX3CR1 cells in the mesenteric lymph nodes and afferent lymph nodes as compared to uninfected controls

abnormal dendritic cell physiology ( J:95694 , J:271242 )

• laminar propria dendritic cells exhibit impaired capacity to traverse the epithelial cell monolayer unlike in heterozygous mice (J:95694)

• laminar propria dendritic cells fail to properly sample E. coli unlike in heterozygous mice (J:95694)

• ileal villi lack intraepithelial dendritic cell extensions unlike in heterozygous mice (J:95694)

• S. typhimurium-infected mice exhibit laminar propria dendritic cells that only form globular structures that fail to cross the epithelium unlike in similarly treated heterozygous mice (J:95694)

• however, sampling of E. coli into the Peyer Patches is normal (J:95694)

• intestinal CX3CR1+ cells show defective dendrite extension after treatment with lactic or pyruvic acid (J:271242)

decreased inflammatory response ( J:271242 )

• intestinal CX3CR1+ cells show defective dendrite extension after treatment with lactic or pyruvic acid

increased susceptibility to bacterial infection induced morbidity/mortality ( J:95694 )

• S. typhimurium-infected mice exhibit a higher organ bacterial load and die within 6 days of infection unlike similarly treated heterozygous and wild-type mice

digestive/alimentary system

abnormal small intestinal villus morphology ( J:95694 )

• ileal villi lack intraepithelial dendritic cell extensions unlike in heterozygous mice

hematopoietic system

increased dendritic cell number ( J:210086 )

• antibiotic-treated mice exhibit increased numbers of all subsets of dendritic cells in the mesenteric lymph nodes as compared to untreated controls

• mice treated with antibiotic and infected with non-invasive Salmonella exhibit increased numbers of only CX3CR1 cells in the mesenteric lymph nodes and afferent lymph nodes as compared to uninfected controls

Genotype
MGI:2670352

hm5

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:84544 )

N • normal dendritic cell migration and IL-12 production in response to a microbial antigen (STAg)

N • normal Langerhans cell migration and APC function in response to contact sensitizer (oxazolone)

decreased monocyte cell number ( J:145036 )

• mice exhibit a reduction in the number of total monocytes compared with wild-type mice

• Gr1^low monocytes are reduced 3-fold compared to in wild-type mice

• however, expression of Tg(S100A8-BCL2)1Lgs restores monocyte numbers

abnormal leukocyte physiology ( J:162714 )

• following kidney ischemia and reperfusion, mice exhibit reduced monocyte egress from the blood into the inflamed kidney compared with similarly treated wild-type mice

impaired macrophage chemotaxis ( J:162714 )

• following kidney ischemia and reperfusion

homeostasis/metabolism

decreased susceptibility to kidney reperfusion injury ( J:162714 )

• following kidney ischemia and reperfusion, mice exhibit decreased kidney injury, tubular cell necrosis, and macrophage recruitment compared with similarly treated heterozygous mice

vision/eye

choroidal neovascularization ( J:127548 )

• following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in similarly treated wild-type mice and choroid neovascularization is twice as much as in similarly treated wild-type mice

abnormal retina morphology ( J:127548 )

• subretinal microglial cells accumulate with age in the retina unlike in wild-type mice

• following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in heterozygous mice at 7 and 14 days post injury

renal/urinary system

decreased susceptibility to kidney reperfusion injury ( J:162714 )

• following kidney ischemia and reperfusion, mice exhibit decreased kidney injury, tubular cell necrosis, and macrophage recruitment compared with similarly treated heterozygous mice

nervous system

nervous system phenotype ( J:84544 )

N • normal neuronal-glial cross talk indicated by microglial response to peripheral nerve injury, 129P2/OlaHsd and C57BL/6 mixed genetic background

cardiovascular system

choroidal neovascularization ( J:127548 )

• following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in similarly treated wild-type mice and choroid neovascularization is twice as much as in similarly treated wild-type mice

hematopoietic system

decreased monocyte cell number ( J:145036 )

• mice exhibit a reduction in the number of total monocytes compared with wild-type mice

• Gr1^low monocytes are reduced 3-fold compared to in wild-type mice

• however, expression of Tg(S100A8-BCL2)1Lgs restores monocyte numbers

abnormal leukocyte physiology ( J:162714 )

• following kidney ischemia and reperfusion, mice exhibit reduced monocyte egress from the blood into the inflamed kidney compared with similarly treated wild-type mice

impaired macrophage chemotaxis ( J:162714 )

• following kidney ischemia and reperfusion

cellular

impaired macrophage chemotaxis ( J:162714 )

• following kidney ischemia and reperfusion

Genotype
MGI:4833985

ht6

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1⁺
• Genetic Background: B6.129P2-Cx3cr1^tm1Litt

nervous system

microgliosis ( J:110266 )

• moderate following LPS exposure

immune system

microgliosis ( J:110266 )

• moderate following LPS exposure

increased susceptibility to experimental autoimmune encephalomyelitis ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis (EAE), mice exhibit intermediate EAE severity (including transient flaccid paresis) compared with homozygous and wild-type mice

• mice treated with anti-NK1.1 antibodies exhibit the same severity of EAE as in homozygous mice following induction of experimental autoimmune encephalomyelitis

behavior/neurological

paresis ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, mice exhibit transient flaccid paresis

hematopoietic system

microgliosis ( J:110266 )

• moderate following LPS exposure

Genotype
MGI:4834138

cx7

• Allelic Composition: Cd1d1^tm1Luc/Cd1d1^tm1Luc; Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: B6.129-Cd1d1^tm1Luc Cx3cr1^tm1Litt

immune system

decreased NK cell number ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis (EAE), mice exhibit a similar reduction in NK1.1/TCRbeta- cells in the central nervous system observed in similarly treated Cx3cr1^tm1Litt compared with similarly treated wild-type mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:129712 )

• mice exhibit the same severity of experimental autoimmune encephalomyelitis as Cx3cr1^tm1Litt homozygotes

behavior/neurological

paralysis ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis, mice exhibit nonremitting spastic paralysis

hematopoietic system

decreased NK cell number ( J:129712 )

• following induction of experimental autoimmune encephalomyelitis (EAE), mice exhibit a similar reduction in NK1.1/TCRbeta- cells in the central nervous system observed in similarly treated Cx3cr1^tm1Litt compared with similarly treated wild-type mice

Genotype
MGI:4834196

cx8

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt; Psen1^tm1Mpm/Psen1^tm1Mpm; Tg(APPSwe,tauP301L)1Lfa/0; Tg(Thy1-YFP)HJrs/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

nervous system

nervous system phenotype ( J:159680 )

N • mice do not exhibit the neuron loss or increase in microglial density and migration velocity observed in Cx3cr1^tm1Litt/Cx3cr1⁺ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

Genotype
MGI:4834197

cx9

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1⁺; Psen1^tm1Mpm/Psen1^tm1Mpm; Tg(APPSwe,tauP301L)1Lfa/0; Tg(Thy1-YFP)HJrs/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

nervous system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

neuron degeneration ( J:159680 )

• of YFP+ layer III neurons at 4 to 6 months

immune system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

hematopoietic system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

Genotype
MGI:4833982

cx10

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt; H2-Ab1^b-tm1Hpl/H2-Ab1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

immune system

abnormal response to infection ( J:95694 )

• S. typhimurium-infected mice exhibit a large number of bacteria in the GFP- phagocyte subset unlike in similarly treated heterozygous mice and fewer bacteria are recovered from lamina propria dendritic cells

Genotype
MGI:5527432

cx11

• Allelic Composition: Ccl2^tm1Rol/Ccl2^tm1Rol; Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J

Retinal lesion in Ccl2^tm1Rol/Ccl2^tm1Rol Cx3cr1^tm1Litt/Cx3cr1^tm1Litt mice

vision/eye

abnormal retina morphology ( J:200877 )

• patches of yellowish/whitish fundus lesions are seen in 17-60% of 12 month old and 30-100% of 18 month old mutants

• majority of lesions are in the temporal area (upper and lower) between the optic disc and equatorial region of the retina, with variable lesion size and lesions are rarely seen in the peripheral retinal areas

• 83-100% of mutants exposed to an approximate 800 lux light 6 hours/day for 6-7 months develop patches of yellowish and whitish lesions compared to 20-25% of wild-type mice

• aged and light-treated mutant retinas exhibit mitochondrial damage, vacuolization, and photoreceptor damage

• however, choroidal neovascularization is not seen in aged or 800 lux light treated mutants and induction of choroidal neovascularization using 532 nm diode laser does not differ from that seen in wild-type mice

abnormal Muller cell morphology ( J:200877 )

• increase in Muller glial activation

abnormal amacrine cell morphology ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting amacrine cell changes in aged mutants

abnormal photoreceptor inner segment morphology ( J:200877 )

• photoreceptor inner segment damage in aged mutants

disorganized photoreceptor outer segment ( J:200877 )

• outer segment disorientation in aged mutants

retina photoreceptor degeneration ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting photoreceptor degeneration

abnormal retina pigmentation ( J:200877 )

• older mutants exhibit pigment loss in RPE cells

retina pigment epithelium atrophy ( J:200877 )

• 33% of 12 month old and 50% of 18 month old mutants exhibit retinal pigment epithelium (RPE) damage, showing altered cell junction, loss of hexagonal tessellation, and uneven distribution of F-actin

• older mutants exhibit multiple vacuoles in the RPE

• all mutants exhibit RPE lesions after light-treatment (800 Lux) compared to 20% of wild-type mice

increased susceptibility to age-related retinal degeneration ( J:200877 )

• mice develop age- and light-mediated retinal damage

abnormal Bruch membrane morphology ( J:200877 )

• increase in Bruch membrane thickness in aged mutants

pigmentation

abnormal retina pigmentation ( J:200877 )

• older mutants exhibit pigment loss in RPE cells

retina pigment epithelium atrophy ( J:200877 )

• 33% of 12 month old and 50% of 18 month old mutants exhibit retinal pigment epithelium (RPE) damage, showing altered cell junction, loss of hexagonal tessellation, and uneven distribution of F-actin

• older mutants exhibit multiple vacuoles in the RPE

• all mutants exhibit RPE lesions after light-treatment (800 Lux) compared to 20% of wild-type mice

nervous system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

abnormal Muller cell morphology ( J:200877 )

• increase in Muller glial activation

abnormal amacrine cell morphology ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting amacrine cell changes in aged mutants

abnormal photoreceptor inner segment morphology ( J:200877 )

• photoreceptor inner segment damage in aged mutants

disorganized photoreceptor outer segment ( J:200877 )

• outer segment disorientation in aged mutants

retina photoreceptor degeneration ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting photoreceptor degeneration

hematopoietic system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

abnormal macrophage physiology ( J:200877 )

• bone marrow derived macrophages exhibit reduced phagocytic activity

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

immune system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

abnormal macrophage physiology ( J:200877 )

• bone marrow derived macrophages exhibit reduced phagocytic activity

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration		DOID:10871	OMIM:PS603075	J:200877

Genotype
MGI:4868437

cx12

• Allelic Composition: Ccr2^tm2.1Ifc/Ccr2^tm2.1Ifc; Cx3cr1^tm1Litt/Cx3cr1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

immune system

abnormal leukocyte physiology ( J:166664 )

• in a mouse model of thioglycollate-induced peritonitis, monocyte recruitment is reduced compared to in similarly treated wild-type mice

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:166664 )

• mice exhibit delayed onset and severity of experimental autoimmune encephalomyelitis with reduced monocyte infiltration into the central nervous system and decreased microglial cell activation compared with similarly treated wild-type mice

hematopoietic system

abnormal leukocyte physiology ( J:166664 )

• in a mouse model of thioglycollate-induced peritonitis, monocyte recruitment is reduced compared to in similarly treated wild-type mice

Genotype
MGI:4868438

cx13

• Allelic Composition: Ccr2^tm2.1Ifc/Ccr2^tm2.1Ifc; Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

immune system

abnormal leukocyte physiology ( J:166664 )

• in a mouse model of thioglycollate-induced peritonitis, monocyte recruitment is reduced compared to in similarly treated wild-type mice

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:166664 )

• mice exhibit delayed onset and severity of experimental autoimmune encephalomyelitis compared with similarly treated wild-type mice

hematopoietic system

abnormal leukocyte physiology ( J:166664 )

• in a mouse model of thioglycollate-induced peritonitis, monocyte recruitment is reduced compared to in similarly treated wild-type mice

Genotype
MGI:4833986

cx14

• Allelic Composition: Cx3cr1^tm1Litt/Cx3cr1^tm1Litt; Tg(SOD1*G93A)1Gur/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

mortality/aging

premature death ( J:110266 )

• decreased survival in male mice compared with Tg(SOD1*G93A)1Gur mice

nervous system

decreased neuron number ( J:110266 )

• compared with Tg(SOD1*G93A)1Gur mice

behavior/neurological

decreased grip strength ( J:110266 )

• male mice exhibit a faster decline in hindlimb grip strength than Tg(SOD1*G93A)1Gur mice

growth/size/body

increased susceptibility to weight loss ( J:110266 )

• male mice exhibit a faster decline in body weight than Tg(SOD1*G93A)1Gur mice