B6.Cg-Tg(GFAP-Ccl2)JE95Rmra/J

Stock number: 014095
Product name: B6.huGFAP-MCP-1 tg+
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

These huGFAP-MCP-1_hi tg⁺ transgenic mice display chronic overexpression of mouse Ccl2 directed primarily to astrocytes of the CNS by the human GFAP promoter.

Detailed description

Mice homozygous for the huGFAP-MCP-1 transgene are viable and fertile, with expression of mouse monocyte chemoattractant protein-1 (MCP-1 or Ccl2) directed primarily to astrocytes of the CNS by the human glial fibrillary acidic protein (GFAP) promoter. Transgene-directed mRNA and protein expression is observed in CNS lysates and astrocyte cultures, as well as in peripheral nerve (such as sciatic; because GFAP is expressed by nonmyelinating Schwann cells). Mice derived from the high-expressing founder line 95 (also called huGFAP-MCP-1_hi tg⁺, huGFAP-CCL2_hi tg⁺, or JE-95 mice) overexpress CCL2 in an astroglial activation-dependent manner. Levels of CCL2 expression in the CNS of huGFAP-CCL2_hi tg⁺ mice were comparable with those observed in CNS tissues from mice with experimental autoimmune encephalomyelitis (EAE). With chronic overexpression of CCL2, aged huGFAP-CCL2_hi tg⁺ mice develop DESMO (delayed encephalopathy/neurodegeneration spontaneously occurring with MCP-1 (CCL2) overexpression). The pathological features of DESMO include motor impairment, reduced life span, modest perivascular cell infiltrates (containing activated macrophages), blood-brain barrier compromise, and widespread microglia activation (as shown by ionized calcium-binding adaptor molecule 1 (IBA-1) immunohistochemistry). In addition, huGFAP-CCL2_hi tg⁺ mice are a model for pertussis toxin-induced reversible encephalopathy dependent on MCP-1 (CCL2) overexpression (PREMO). The donating investigator also reports that transgenic mice exhibit the same monophasic EAE phenotype as C57BL/6 inbred mice. These huGFAP-CCL2_hi tg⁺ transgenic mice may be useful for studying neurodegeneration, innate and adaptive immune system, inflammation, and demyelinating autoimmune disease (such as multiple sclerosis and EAE protocols).

Development

The huGFAP-MCP-1 transgene was designed with the 2.2 kb promoter region from the human GFAP gene upstream of a mouse 1.7 kb mouse Ccl2 genomic DNA sequence. This transgene was injected into (SWR/J x SJL/J)F1 eggs (SWXJ (H-2^q,s; generated by mating SWR/J (H-2^q) females with SJL/J (H-2^s) males)). The resulting transgenic offspring were bred to C57BL/6J mice to establish founder line 95 (JE-95). Mice from this founder line were found to have the highest expression of the transgene, and were termed huGFAP-MCP-1_hi tg+ mice (also called huGFAP-CCL2_hi tg+ mice or JE-95 mice). These mice were then backcrossed to C57BL/6J mice for at least eight generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tg(GFAP-Ccl2)JE95Rmra
Name: transgene insertion JE95, Richard Ransohoff
MGI accession ID: MGI:4843357
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: huGFAP-CCL2hi tg+; huGFAP-MCP-1 tg+; huGFAP-MCP-1hi tg; JE95; JE-95
Marker symbol: Tg(GFAP-Ccl2)JE95Rmra
Marker name: transgene insertion JE95, Richard Ransohoff
Chromosome: UN
Strain of origin: (SWR/J x SJL/J)F1
Expressed genes: Ccl2,chemokine (C-C motif) ligand 2,mouse, laboratory
Molecular note: The huGFAP-MCP-1 transgene was designed with the 2.2 kb promoter region from the human GFAP gene upstream of a mouse 1.7 kb mouse Ccl2 genomic DNA sequence. Line JE95 exhibited the highest expression level.