NOD.129-Ica1^tm1Mdos/MdosJ

Stock number: 005080
Product name: NOD.ICA1
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These Ica1 knock-out mice develop mild salivary gland infiltrations and development of spontaneous diabetes is slightly delayed.

Detailed description

Ica1^tm1Mdos homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Ica1 by western blot analysis. Ica1^tm1Mdos homozygous animals develop mild salivary gland infiltrations with progression of disease 55%-65% slower than progression of submandibular gland monouclear foci in wildtype and heterozygote controls. Dacryodenitis was undetectable in 35-40 week old male Ica1^tm1Mdos homozygous mice compared to 64% of wildtype and 58% of heterozygotes similarly aged (Winer et al., 2002). Development of spontaneous diabetes is slightly delayed in this stock (by 4 weeks) and incidence is modestly diminished (65% incidence in females after 36 weeks versus 85% in wild-type NOD females). Ica1^tm1Mdos homozygous females are significantly protected from cyclophosphomide (CY) induced diabetes (10% in females post CY treatment versus 70% incidence in female heterozygote controls). Many unmanipulated Ica1^tm1Mdos homozygous females not diagnosed as diabetic died unexpectedly of unknown causes, resulting in a 35% death rate by 50 weeks of age (Winer et al., 2002).

This model provides a tool for studying the role of Ica1 as a beta cell autoantigen in the NOD mouse model of Type 1 diabetes and sialadenitis and dacryoadenitis.

Development

A construct containing a tTA-neo cassette replaced the Tep69 epitope of exon 2 region of Islet cell antigen 1,Ica1, commonly referred to as Ica69 and cloned from a 129/Sv mouse genomic library and transfected into R1 ((129X1/SvJ x 129S1/Sv)F1-Kitl+) embryonic stem cells (ES cells). These ES cells were injected into NOD/Lt blastocysts. To establish a colony with germ line transmission, chimeric mice were backcrossed to NOD/Lt. In 2004, The Jackson Laboratory received NOD.129-Ica1^tm1Mdos/MdosJ at generation N20. These animals were subsequently backcrossed once to NOD/LtJ prior to intercrossing.

Allele

Symbol: Ica1^tm1Mdos
Name: targeted mutation 1, H Michael Dosch
MGI accession ID: MGI:2662437
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ica1
Marker name: islet cell autoantigen 1
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The gene was disrupted by insertion of a tTA-neo cassette into the Tep69 epitope sequence of exon 2 via homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of brain and salivary gland proteins.