B6.Cg-Tg(Cd3d-Il5)NJ.1638Nal/JleeJ

Stock number: 036943
Product name: NJ.1638
Research areas: Hematological Research, Research Tools

Description

NJ.1638 transgenic mice express murine IL-5 under the control of the CD3 delta promoter and enhancer. They develop hypereosinophilia where eosinophils are 35-65 percent of the white blood cells in circulation. Mice develop age related dermatitis, lymphocyte expansion, and splenomegaly with ossification and extramedullary eosinophilpoiesis. These mice are useful to study eosinophilic diseases and as a source of differentiated blood eosinophils.

Detailed description

NJ.1638 transgenic mice express murine interleukin 5 (Il5) controlled by the promoter and enhancer region of the murine CD3 delta promoter (Cd3d). All CD3delta expressing T cells will express IL-5 in these mice. IL-5 is a cytokine that plays a major role in the regulation of eosinophilpoiesis, differentiation, and survival. Serum levels of IL-5 range from 400-800 pg/ml. Since the original publication (described in Lee NA et al. J Immunol Feb 1997) the features of these mice are modified here to reflect the current knowledge gained on the strain over the last 15 years. These mice display hyperosinophilia with 35-65% of the white blood cells are differentiated eosinophils. Total white blood cell numbers increase with age and by 4 months of age there is expansion of B cells and by 7 months both B and T cells expand. Approximately 25% of mice develop lymphoma like masses by the age of 10 months. 10% of mice develop rectal prolapse and ~25% of transgenic animals are morbid by 12 months of age. These mice display infiltration of eosinophils in nearly all organ systems, although inflammation does not always correlate with an ongoing inflammation process. Dermatitis of the skin is the most common occurrence of disease with these mice and is often treatable with antibiotic ointment. These mice develop significant splenomegaly and the spleen is a site of extramedullary eosinophilpoiesis in these mice. The spleen develops ossification/bone growth with aging for unknown reasons. While both male and female mice are viable and fertile, there is a higher risk of physical birthing difficulties for the female mice as compared to C57BL/6J mice. These mice, particularly when studied prior to 7 months of age, are useful to models of eosinophilic disease and for isolation of a pure population of eosinophils from the blood. When crossed to eosinophil deficient PHIL mice (Stock No. 036945), these mice are eosinophil-deficient, despite the high level of IL-5 production (Ochkur S. et al. J Immunol June 2007).

Hemizygous mice are viable and fertile. The donating laboratory did not attempt to make mice homozygous for the transgene.

Development

This strain contains a 5.5-kb construct of murine interleukin 5 (Il5) which includes the start codon followed by the native intronic and exon sequences up to 1.2kb of the 3' flanking sequence of murine IL-5. A combined Cd3d promoter and enhancer was used to direct expression of the IL-5 gene. The Cd3d promoter and enhancer is comprised of a fusion of a Nar1-EcoR1 fragment of the CD3d promoter site connected to a Bcl1-Bcl1 fragment of the DNase I hypersensitive enhancer area of the 3' end of the CD3d gene that acts as a regulatory element for T -cell specificity. Thus, CD3d directs expression of the murine IL-5 from T cells. This transgene was microinjected into fertilized (CBA/CaJ x C57BL/6J)F1 x C57BL/6J oocytes. NJ.1638 mice from founder line NJ.1638, with 5 copies of the transgene, were subsequently maintained by breeding transgenic mice with C57BL/6J inbred mice for at least 20 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(Cd3d-Il5)NJ.1638Nal
Name: transgene insertion NJ.1638, Nancy A Lee
MGI accession ID: MGI:3767981
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: IL-5tg; NJ.1638
Marker symbol: Tg(Cd3d-Il5)NJ.1638Nal
Marker name: transgene insertion NJ.1638, Nancy A Lee
Marker synonyms: NJ.1638
Chromosome: UN
Strain of origin: (CBA/J x C57BL/6J)F1 x C57BL/6J
Molecular note: This construct was created by fusing in frame a 170-bp fragment from the 5' end of IL-5 cDNA with the remaining portion of the genomic IL-5 gene. This minigene has no upstream flanking sequences but has all of the introns of the gene as well as 1 .2 kb of downstream flanking sequence. To drive expression of the transgene in T cells, a promoter and tissue-specific enhancer derived from the murine CD3d gene was included upstream. Three founding lines (NJ.759, NJ.1638, NJ.1643) were created with one chosen for further studies. High levels of circulating IL-5 were detected in the sera of transgenic mice but not in wild-type mice.