Mouse Genome Informatics
hm1
    Il6tm1Mur/Il6tm1Mur
B6.129P2(B6)-Il6tm1Mur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• ethanol-fed homozygotes fail to exhibit a significant decrease in CFU-osteoblast formation in long-term marrow cultures, but exhibit a 60% reduction in osteoblast culture calcium retention relative to control-fed homozygotes
• ethanol-fed homozygotes fail to exhibit increased osteoclast surface, as determined by femur histomorphometry
• in culture, ethanol-fed homozygotes show reduced numbers of CFU-fibroblasts with osteoclast-like cells relative to control diet-fed homozygotes
• ethanol-fed homozygotes fail to exhibit increased CFU-GM formation, osteoclastogenesis, and Tnfsf11 (RANKL) mRNA expression in the bone marrow
• male homozygotes fed a 5% ethanol liquid diet for 4 months fail to exhibit a significant decrease in whole-body and femoral bone mineral density (BMD), indicating protection from ethanol-induced bone loss
• in accord with BMD data, ethanol-fed homozygotes fail to exhibit elevated urinary levels of deoxypyridinolines, an indicator of bone resorption
• no hepatic inflammation, cirrhosis or changes in gonadal hormone levels are observed
• ethanol-fed homozygotes fail to exhibit reduced cancellous bone volume and trabecular width or increased trabecular spacing, as determined by femur histomorphometry

nervous system
• mutant dopamine neurons are more vulnerable to MPTP-induced dopaminergic degeneration relative to wild-type
• in contrast, striatal astrogliosis induced by MPTP-lesioning appears to be similar in wild-type and mutant mice
• despite normal reactive astrogliosis in mutant substantia nigra pars compacta, MPTP-lesioned homozygotes exhibit impaired microgliosis, with complete absence of reactive microglia at 7 days post-lesion
• at 7 days post-lesion, mutant microglia fail to mount a robust, persistent reactive microgliosis in response to MPTP-driven injury in the substantia nigra pars compacta (SNpc)
• concomitant with a decline in reactive microgliosis, microglial expression of inducible nitric oxide synthase (Nos2) is diminished in MPTP-lesioned SNpc
• after a single injection of MPTP (30 mg/kg), homozygotes exhibit a significantly greater striatal dopamine depletion relative to wild-type mice
• loss of striatal dopamine is MPTP dose-dependent, with doses of 10-30 mg/kg resulting in a 20-25% increase in dopamine depletion in mutant striatum, and doses of 40 mg/kg being lethal in mutant, but not in wild-type mice
• after a single injection of MPTP (30 mg/kg), homozygotes show a significantly greater loss of TH+ cells in the substantia nigra pars compacta relative to wild-type mice
• at 7 days post MPTP lesion, homozygotes exhibit normal reactive astrogliosis (i.e. 50-55% increase in reactive astrocyte numbers) in the substantia nigra pars compacta (SNpc)
• in contrast, reactive microgliosis is compromised in MPTP-lesioned SNpc

immune system
• ethanol-fed homozygotes fail to exhibit increased osteoclast surface, as determined by femur histomorphometry
• in culture, ethanol-fed homozygotes show reduced numbers of CFU-fibroblasts with osteoclast-like cells relative to control diet-fed homozygotes
• despite normal reactive astrogliosis in mutant substantia nigra pars compacta, MPTP-lesioned homozygotes exhibit impaired microgliosis, with complete absence of reactive microglia at 7 days post-lesion
• at 7 days post-lesion, mutant microglia fail to mount a robust, persistent reactive microgliosis in response to MPTP-driven injury in the substantia nigra pars compacta (SNpc)
• concomitant with a decline in reactive microgliosis, microglial expression of inducible nitric oxide synthase (Nos2) is diminished in MPTP-lesioned SNpc
• ethanol-fed homozygotes fail to exhibit increased CFU-GM formation, osteoclastogenesis, and Tnfsf11 (RANKL) mRNA expression in the bone marrow
• MPTP-lesioned homozygotes show dysregulated neuroinflammation i.e. impaired reactive microgliosis and astrocyte-microglia interactions, resulting in increased nigrostriatal vulnerability to neurotoxicant

hematopoietic system
• ethanol-fed homozygotes fail to exhibit increased osteoclast surface, as determined by femur histomorphometry
• in culture, ethanol-fed homozygotes show reduced numbers of CFU-fibroblasts with osteoclast-like cells relative to control diet-fed homozygotes
• despite normal reactive astrogliosis in mutant substantia nigra pars compacta, MPTP-lesioned homozygotes exhibit impaired microgliosis, with complete absence of reactive microglia at 7 days post-lesion
• at 7 days post-lesion, mutant microglia fail to mount a robust, persistent reactive microgliosis in response to MPTP-driven injury in the substantia nigra pars compacta (SNpc)
• concomitant with a decline in reactive microgliosis, microglial expression of inducible nitric oxide synthase (Nos2) is diminished in MPTP-lesioned SNpc
• ethanol-fed homozygotes fail to exhibit increased CFU-GM formation, osteoclastogenesis, and Tnfsf11 (RANKL) mRNA expression in the bone marrow

homeostasis/metabolism
• mutant dopamine neurons are more vulnerable to MPTP-induced dopaminergic degeneration relative to wild-type
• in contrast, striatal astrogliosis induced by MPTP-lesioning appears to be similar in wild-type and mutant mice
• after a single injection of MPTP (30 mg/kg), homozygotes exhibit a significantly greater striatal dopamine depletion relative to wild-type mice
• loss of striatal dopamine is MPTP dose-dependent, with doses of 10-30 mg/kg resulting in a 20-25% increase in dopamine depletion in mutant striatum, and doses of 40 mg/kg being lethal in mutant, but not in wild-type mice

cellular
• mutant dopamine neurons are more vulnerable to MPTP-induced dopaminergic degeneration relative to wild-type
• in contrast, striatal astrogliosis induced by MPTP-lesioning appears to be similar in wild-type and mutant mice
• ethanol-fed homozygotes fail to exhibit a significant decrease in CFU-osteoblast formation in long-term marrow cultures, but exhibit a 60% reduction in osteoblast culture calcium retention relative to control-fed homozygotes
• ethanol-fed homozygotes fail to exhibit increased osteoclast surface, as determined by femur histomorphometry
• in culture, ethanol-fed homozygotes show reduced numbers of CFU-fibroblasts with osteoclast-like cells relative to control diet-fed homozygotes


Mouse Genome Informatics
hm2
    Il6tm1Mur/Il6tm1Mur
involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 8 weeks post-infection, lymphocyte preps isolated from T. gondii-infected wild-type brains exhibit higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells but lower ratios of CD8+ alpha/beta cells relative to those found in infected mutant brains
• in contrast, the relative % of T cell subsets in spleens of T. gondii-infected homozygotes are comparable to those of infected wild-type mice at 8 weeks post-infection
• at 8 weeks post-infection, lymphocyte preps isolated from T. gondii-infected mutant brains show absence of NK1.1+ cells, suggesting that the primary source of IFN-gamma in infected brains is T cells
• at 8 weeks post-infection, T. gondii-infected mutant brains show significantly decreased IFN-gamma mRNA levels relative to infected wild-type brains
• no significant differences in IL-10, IL-4 or TNF mRNA levels are observed, although IL-10 mRNA levels tend to be higher in infected mutant brains
• at 8 weeks post-infection, T. gondii-infected mutant brains display fewer numbers of inflammatory cells in many tachyzoite-containing areas relative to wild-type brains
• at 4 and 8 weeks post-infection, homozygotes exhibit impaired resistance to infection with T. gondii (ME49 strain), associated with increased numbers of tachyzoites and brain cysts, as well as increased inflammation areas and parasitophorus vacuoles containing tachyzoites relative to infected wild-type mice
• in homozygotes, tachyzoites are frequently associated with only a few inflammatory cells
• unlike wild-type, brains of infected homozygotes exhibit large areas of necrosis caused by proliferation of tachyzoites

nervous system
• at 8 weeks post-infection, T. gondii-infected mutant brains display fewer numbers of inflammatory cells in many tachyzoite-containing areas relative to wild-type brains

hematopoietic system
• at 8 weeks post-infection, lymphocyte preps isolated from T. gondii-infected wild-type brains exhibit higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells but lower ratios of CD8+ alpha/beta cells relative to those found in infected mutant brains
• in contrast, the relative % of T cell subsets in spleens of T. gondii-infected homozygotes are comparable to those of infected wild-type mice at 8 weeks post-infection
• at 8 weeks post-infection, lymphocyte preps isolated from T. gondii-infected mutant brains show absence of NK1.1+ cells, suggesting that the primary source of IFN-gamma in infected brains is T cells

homeostasis/metabolism
• at 8 weeks post-infection, T. gondii-infected mutant brains show significantly decreased IFN-gamma mRNA levels relative to infected wild-type brains
• no significant differences in IL-10, IL-4 or TNF mRNA levels are observed, although IL-10 mRNA levels tend to be higher in infected mutant brains


Mouse Genome Informatics
hm3
    Il6tm1Mur/Il6tm1Mur
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• homozygotes show no significant differences in total numbers or subtypes of B cells, T cells, NK cells, macrophages, or neutrophils relative to wild-type mice (J:25684)
• homozygotes exhibit normal NK cell activation, IGN-gamma production and macrophage activation (upregulation of MHC class II and downregulation of F4/80) during listeriosis (J:25684)
• in addition, macrophages isolated from Listeria-infected homozygotes display normal NO production (J:25684)
• homozygotes fail to mount peripheral blood neutrophilia in response to listeriosis, whereas wild-type mice show prominent neutrophilia at 24 and 48 hrs post-infection
• homozygotes succumb to sublethal doses of Listeria monocytogenes, with a 50-60% mortality rate within 7 days of inoculation, massive replication of bacteria in spleen and liver at 2 and 3 days post-infection, and multiple inflammatory foci with notable necrosis and numerous live bacteria
• notably, neutrophil-depleted wild-type and mutant mice show similar levels of sensitivity to L. monocytogenes infection
• exogenous administration of rIL-6 completely restores survival to wild-type levels, and confers significant levels of protection to animals devoid of lymphocytes, but not devoid of neutrophils, during listeriosis

hematopoietic system
• homozygotes fail to mount peripheral blood neutrophilia in response to listeriosis, whereas wild-type mice show prominent neutrophilia at 24 and 48 hrs post-infection


Mouse Genome Informatics
ht4
    Il6tm1Mur/Il6+
B6.129P2(B6)-Il6tm1Mur
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• after a single injection of MPTP (30 mg/kg), heterozygotes exhibit a significantly greater striatal dopamine depletion relative to wild-type mice, suggesting a gene dosage effect

homeostasis/metabolism
• after a single injection of MPTP (30 mg/kg), heterozygotes exhibit a significantly greater striatal dopamine depletion relative to wild-type mice, suggesting a gene dosage effect