Mouse Genome Informatics
hm1
    Gfaptm1Pkny/Gfaptm1Pkny
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• homozygotes display normal histological CNS architecture relative to wild-type controls (J:25093)
• mutant brains contain normal numbers of astroglial cells in the hippocampus, as shown by comparative GFAP and S-100 immunostaining (J:25093)
• mutant enteric glial cells in the myenteric plexi of the ileum and colon are GFAP-negative but show normal S-100 immunostaining (J:25093)
• no impairment of the blood-brain barrier function is observed (J:25093)
• at 4 days after fine needle brain injury, homozygotes display a reactive gliosis that is qualitatively similar to that observed in wild-type brains (J:25093)
• astrocyte motility and morphology is similar to wild-type cells (J:125659)
• unlike wild-type, mutant astrocytes in the hipocampus and in the white matter of the spinal cord are completely devoid of 10 nm thick intermediate filaments (J:25093)
• mutant astrocytes show reduced numbers of intermediate filaments relative to wild-type (J:125659)

cellular
N
• astrocytes are morphologically similar to wild-type (J:125659)
• astrocyte motility in culture is similar to wild-type (J:125659)

behavior/neurological
N
• homozygotes are viable, fertile and exhibit normal motility, learning and memory relative to wild-type littermates (J:25093)

digestive/alimentary system
N
• homozygotes exhibit normal intestinal peristalsis and fecal composition, indicating that mutant myenteric plexi are functionally intact (J:25093)


Mouse Genome Informatics
cx2
    Gfaptm1Pkny/Gfaptm1Pkny
Vimtm1Cba/Vimtm1Cba

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in the granular layer of the dentate gyrus of 18-month old null mice, there is a 36% in formation of new neurons compared to wild-type
• 18-month old null mice show higher levels of cell proliferation (34%) in the granular layer of the dentate gyrus than in wild-type

cellular
• in the granular layer of the dentate gyrus of 18-month old null mice, there is a 36% in formation of new neurons compared to wild-type


Mouse Genome Informatics
cx3
    Gfaptm1Pkny/Gfaptm1Pkny
Ppt1tm1Hof/Ppt1tm1Hof
Vimtm1Cba/Vimtm1Cba

involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• mutants exhibit immune cell infiltration in the brain, with an increase in CD45+ leukocytes, CD3+ T-cells, and CD68+ large monocytes; immune cell infiltration in triple mutants is similar to that in single Ppt1 homozygotes
• triple mutants exhibit earlier and more rapid progression of neurodegenerative disorder resembling infantile neuronal ceroid lipofuscinosis than single Ppt1 homozygotes
• mutants exhibit a 3.3-fold increase in autofluorescent accumulation in the brain compared to wild-type mice
• decrease in brain weight by 26.2% is seen by 6 months of age
• atrophy of the primary visual cortex
• at 6 months of age, 28.9% decrease in cortical thickness
• by 5 months of age, brain atrophy is apparent
• mutants exhibit progressive neurodegeneration, with degenerating neurons within the cortex, thalamus, hippocampus, and cerebellum at 5 months of age
• at 5 months of age, extent of neurodegeneration is similar to that seen in single Ppt1 mutants at 7 months of age

immune system
• mutants exhibit elevated cytokine levels, starting at 1 month of age, with an increase in the number of different cytokines elevated by 3 and 6 months of age
• at 1 month of age, cytokines RANTES and oncostatin-M are elevated compared to wild-type or single Ppt1 homozygotes
• at 3 months of age, IFN-gamma, TNF-alpha, oncostatin-M, lymphoactin, GM-CSF, RANTES, IP-10, MIP-1beta, MIP-2, MCP-1, MCP-3, and MCP-5 are elevated compared to wild-type mice; more cytokines and chemokines are elevated at 3 months of age than in single Ppt1 homozygotes.
• mutants exhibit immune cell infiltration in the brain, with an increase in CD45+ leukocytes, CD3+ T-cells, and CD68+ large monocytes; immune cell infiltration in triple mutants is similar to that in single Ppt1 homozygotes

homeostasis/metabolism
• mutants exhibit elevated cytokine levels, starting at 1 month of age, with an increase in the number of different cytokines elevated by 3 and 6 months of age
• at 1 month of age, cytokines RANTES and oncostatin-M are elevated compared to wild-type or single Ppt1 homozygotes
• at 3 months of age, IFN-gamma, TNF-alpha, oncostatin-M, lymphoactin, GM-CSF, RANTES, IP-10, MIP-1beta, MIP-2, MCP-1, MCP-3, and MCP-5 are elevated compared to wild-type mice; more cytokines and chemokines are elevated at 3 months of age than in single Ppt1 homozygotes.

Mouse Models of Human Disease
OMIM IDRef(s)
Ceroid Lipofuscinosis, Neuronal, 3; CLN3 204200 J:177265


Mouse Genome Informatics
cx4
    Gfaptm1Pkny/Gfaptm1Pkny
Vimtm1Cba/Vimtm1Cba

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• after cortical injury, mutants show comparable cell proliferation in injured region to controls (J:124385)
• after a cortical stab wound was made, many mutants show extensive intracranial bleeding at site of injury 3 days after wounding, in contrast to controls and single mutants which do not display such extensive bleeding
• in detached retinas of mutants 3 days after surgically-induced retinal detachment (RD), few apoptotic photoreceptor cells are detected compared to detached retinas of control mice
• cells show absence of intermediate filaments relative to wild-type
• astrocytes are smaller(35%) and exhibit fewer and shorter processes than wild-type cells
• 3 days following surgically-induced retinal detachment (RD), mutant retinas show significantly suppressed reactive gliosis in inner nuclear layer (INL) compared to wild-type after RD
• many vessels in brain and spinal cord appear dilated compared to controls
• dorsal spinal cord shows an unusually deep indentation in mutants compared to wild-type
• scar tissue induced by incision in dorsal funiculus is less dense and contains fissures with blood, tissue fluid or debris, compared to wild-type mice 2 days or 2 weeks after surgery
• astrocytes display reduction of cell motility relative to wild-type
• rate of diffusion of astrocytes is decreased

vision/eye
N
• 7 days after RD, thickness of outer nuclear layer (ONL) is unchanged, in contrast to controls after RD where a 55% reduction in ONL thickness is observed (J:123278)

immune system
• after RD, retinas of mutants exhibit suppression of monocyte infiltration compared to wild-type retinas after RD; in controls, 3 days after RD, significant numbers of monocytes are detected in outer plexiform layer (OPL), mainly attached to photoreceptor outer segments in subretinal space (SRS)

cardiovascular system
• after a cortical stab wound was made, many mutants show extensive intracranial bleeding at site of injury 3 days after wounding, in contrast to controls and single mutants which do not display such extensive bleeding
• many vessels in brain and spinal cord appear dilated compared to controls

muscle
• many vessels in brain and spinal cord appear dilated compared to controls

cellular
• in detached retinas of mutants 3 days after surgically-induced retinal detachment (RD), few apoptotic photoreceptor cells are detected compared to detached retinas of control mice