STOCK Tg(B19-RNAi:Il3)241Ckn/J

Stock number: 002182
Product name: AS-IL-3
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Detailed description

These AS-IL-3 mice express a transgene containing the full length, 990-bp mouse interleukin 3 cDNA and develop a fatal lymphoproliferative syndrome and progressive neurologic dysfunction.

Development

The transgenic construct consists of a 990 bp fragment corresponding to the full length antisense murine Il3 cDNA under the control of the B19 parvovirus promoter and a 3’ T cell dominant control region from the 3’ end of the human CD2 gene. The construct was injected into fertilized eggs from FVB/N female mice mated to CB6F1 males in the laboratory of Dr. Cynthia Dunbar at the NIH. Founder line 241 exhibits the highest penetrance of the two phenotypes. This transgenic founder was crossed to a strain designated KIV to generate heterozygosity at the Hprt locus. (Unfortunately, we do not have information regarding the origins or characteristics of strain KIV.) The strain was then backcrossed to FVB/N for three generations. The donating investigator reports that these transgenic mice manifest a phenotype identical to the strain reported in Cockayne DA et al. Blood 84:2699 (1994). In 1993, The Jackson Laboratory imported this line and mated transgenic males to FVB/NMob females for an additional backcross. The line was cryopreserved in 1994.

Allele

Symbol: Tg(B19-RNAi:Il3)241Ckn
Name: transgene insertion 241, Debra A Cockayne
MGI accession ID: MGI:3689387
Generation method: Transgenic
Attributes: Knockdown
Marker symbol: Tg(B19-RNAi:Il3)241Ckn
Marker name: transgene insertion 241, Debra A Cockayne
Chromosome: UN
Strain of origin: FVB/N X (BALB/c x C57BL/6)F1
Expressed genes: Il3_antisense,antisense RNA,
Molecular note: This transgene consists of the full length, 990-bp mouse interleukin 3 cDNA, in reverse (antisense) orientation, under control of the B19 parvovirus promoter and a T-cell dominant control region from the 3' end of the human CD2 gene. A human beta-globin gene segment including the 3' end of exon 2, all of intron 2 and exon 3, the polyadenylation signal and some 3' flanking DNA is present just downstream of the Il3 sequence. Interleukin 3 antisense RNA is detected by RT-PCR analysis in mature CD3⁺ T lymphocytes of transgenic animals both with lymphoproliferation and with no disease phenotype, in transgenic B220⁺IgM^- pre-B cells, and in brains of both asymptomatic and neurologically affected transgenic mice. Il3 antisense transcripts are present in cultured splenocytes from asymptomatic transgenic mice following in vitro concanavalin A (ConA) stimulation, and ELISA of supernatants from these cultures demonstrates a 5-fold reduction in interleukin 3 secretion compared to similar cultures of control splenocytes.
General note: Of 5 transgenic founder lines, two exhibited no abnormal phenotype and were not further characterized. One of the other founder mice died of neurologic disease at 3 months, without having bred. Founders 241 and 244 transmitted the transgene and both the lymphoproliferative and neurologic phenotypes to their progeny. The pathology of the neurologic and of the lymphoproliferative disorders differs between the two lines only in penetrance and in age of onset (3-6 months for line 241 compared to 6-12 months for line 244).