Female Stat4 knock-out mice exhibit significantly decreased diabetes compared to female NOD controls.
Dr. Jeffrey A. Bluestone, University of California, San Francisco
Genetic Background | Generation |
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001976 NOD/ShiLtJ |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Stat4 | signal transducer and activator of transcription 4 |
Stat4tm1Gru homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. NOD female mice homozygous for the Stat4tm1Grumutation are reported to exhibit significantly decreased diabetes, approximately 20% diabetic by 30 weeks of age, compared to Approximately 45% of the female NOD controls (Chatenoud et al, 2001). There is no detectable STAT4 protein in purified splenocytes. IL12 mediated interferon-gamma secretion, natural killer cytolytic function and Th1 cell differentiation are defective. Analysis by ELISA indicates reduction of interferon gamma and IL2 when compared to diabetic and non-diabetic NOD. Phenotype of this stock is similar to the Yang et al, model reported to have a shorter congenic interval on Chromosome 1 including an NOD-derived Idd5. This model is useful for looking at the role of IL12 in diabetes development.
The Stat4tm1Gru mutation was backcrossed to NOD for 8 generations prior to intercrossing. In 2003, The Type 1 Diabetes Resource received NOD.129S2-Stat4tm1Gru at generation N8F8. Our "Idd Sweep" and "Chromosome of Interest" allele testing showed this strain had 129 or C57BL/6-derived markers D1Mit236 (Chr1; 25.7cM) through D1Mit36 (Chr1; 92.3cM). Stat4 (Chr1; 25.9cM) and Idd5(Chr1; 40cM) are located within this interval. Additionally, there was a 129 derived segment on Chromosome 10, D10Mit87 (Chr10; 16cM) through D10Mit20(Chr10; 35cM). These animals were backcrossed 2 times to NOD/LtJ (JR# 1976) prior to making homozygous. Our allele testing indicates these animals continue to carry the Chromosome 1, 129 or C57BL/6 derived markers (D1Mit236 - D1Mit36), including Idd5, however, Chromosome 10 markers (D10Mit87-D10Mit20) are NOD derived.
Allele Name | targeted mutation 1, Michael J Grusby |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Stat4- |
Gene Symbol and Name | Stat4, signal transducer and activator of transcription 4 |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 1 |
Molecular Note | The exon encoding amino acids 263 through 314 was disrupted by the insertion of a neomycin selection cassette. The encoded protein was undetectable in the thymi and lymph nodes of homozygous mutant mice by immunoblot analysis. |
Mutations Made By | Dr. Michael Grusby, Harvard Medical School |
When using the NOD.Stat4 knockout mouse strain in a publication, please cite the originating article(s) and include JAX stock #004671 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Stat4<tm1Gru>, 1 pair minimum |
Frozen Mouse Embryo | NOD.129S2-Stat4<tm1Gru>/JbsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129S2-Stat4<tm1Gru>/JbsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129S2-Stat4<tm1Gru>/JbsJ Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | NOD.129S2-Stat4<tm1Gru>/JbsJ Frozen Embryos | $3373.50 |
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