NOD.129S2-Stat4^tm1Gru/JbsJ

Stock number: 004671
Product name: NOD.Stat4 knockout
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

Female Stat4 knock-out mice exhibit significantly decreased diabetes compared to female NOD controls.

Detailed description

Stat4^tm1Gru homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. NOD female mice homozygous for the Stat4^tm1Grumutation 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.

Development

The Stat4^tm1Gru mutation was backcrossed to NOD for 8 generations prior to intercrossing. In 2003, The Type 1 Diabetes Resource received NOD.129S2-Stat4^tm1Gru 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

Symbol: Stat4^tm1Gru
Name: targeted mutation 1, Michael J Grusby
MGI accession ID: MGI:1857248
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Stat4-
Marker symbol: Stat4
Marker name: signal transducer and activator of transcription 4
Chromosome: 1
Strain of origin: 129S2/SvPas
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.