Ins1tm1Jja homozygotes are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Ins1 in the pancreas by RT-PCR and similar levels of insulin auto-antibodies develop in NOD.129S2(B6)-Ins1tm1Jja homozygotes as are found in NOD controls. However, neither homozygous nor heterozygous males develop diabetes, compared with >20% of wild-type littermates, and less than 5% of the Ins1tm1Jja homozygous females and 40% of the heterozygous females become diabetic compared with >80% of wild-type females when followed for 1 year. Histological evaluation found 48 week old homozygous and heterozygous males to have either minimal periinsulitis or no insulitis. Heterozygous females had more extensive insulitis than heterozygous males and homozygous females had minimal intra-ductal infiltrates and no insulitis, whereas wild type littermates had severe insulitis by 37 weeks of age (Moriyama et al, 2003).
NOD.129S2(B6)-Ins1tm1Jja/GseJ (Stock No. 005035) is useful for studying insulin autoantigens and their role in the autoimmune process leading to Type 1 Diabetes.
A construct containing a neomycin expression cassette replacing most of the Ins1 coding sequences, was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were initially mated to C57BL/6 and subsequently intercrossed to generate homozygotes (Duvillie et al, 1997). Dr. George Eisenbarth s laboratory received B6.129S2-Ins1tm1Jja from Dr. Jacques Jami and backcrossed this mutation to NOD for 11 generations (Moriyama et al, 2003). In 2004, N11 mice were received at The Jackson Laboratory, backcrossed to NOD/LtJ once, and then maintained homozygote x homozygote.
|Allele Name||targeted mutation 1, Jacques Jami|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ins1, insulin I|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The majority of the coding region was replaced with a neomycin selection cassette. RT-PCR analysis showed an absence of transcript in homozygous mutant mice.|
|Mutations Made By|| |
Jacques Jami, INSERM
When using the NOD.Ins1null mouse strain in a publication, please cite the originating article(s) and include JAX stock #005035 in your Materials and Methods section.