NOD.B6-(D6Mit254-D6Mit339)/CarJ

Stock number: 004482
Product name: NOD.Nk1.1
Research areas: Diabetes and Obesity Research

Description

These mice harbor a C57BL/6JOrl chromosome segment containing the Klrb1c^a allele that determines the Nk1.1 antigen on natural killer cells. Diabetes incidence is significantly decreased in these mice.

Detailed description

Klrb1c^a homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Diabetes incidence as reported by donating investigator and confirmed in the T1DR, prior to shortening the congenic interval, is significantly decreased (30% females and 0% males at 30 weeks of age) as compared to standard NOD (NK1.2) controls (85% females and 60% males at 30 weeks of age) . FACS analysis of NKT cells derived from thymus or spleen of NOD animals homozygous for this genomic segment revealed the presence of NK1.1+/TCR alpha beta +, V beta8+ and CD44+, but at lower levels than in C57BL/6 controls. NK cells of NOD.B6-(D6Mit254-D6Mit14) exhibit an equivalent number of NK1.1/DX5 double positive cells when compared to C57BL/6. Histological examination of 10-12 week old animals indicates no significant difference in insulitis severity between NOD.B6-(D6Mit254-D6Mit14) and NOD control islets (Carnaud et al, 2001). Confirming the published report that insulitis development in NK1.1 congenics is not significantly different from control NOD (NK1.2+)(Carnaud et al, 2001), sampling of non-diabetic NOD.NK1.1 congenic mice in the TIDR at 30 wk of age also showed extensive insulitis. This model is useful for looking at the role of natural killer cells in autoimmune diseases such as Type 1 Diabetes.

Development

A Chromosome 6 genomic segment from C57BL/6JOrl originally reported to span D6Mit254 through D6Mit14 and containing Klrb1c^a (commonly referred to as NK1.1) was transferred through 10 generations of backcrossing to NOD/Necker (Carnaud et al, 2001). In 2002, this strain arrived at TJL at N10F?. Further a selected genome scan ("Idd sweep" and "Chromosome of interest") indicated that some animals of this strain were heterozygous for a C57BL/6-derived marker on Chromosome 3(D3Mit95) as well as carrying a longer Chromosome 6 congenic interval (D6Mit328 - D6Mit15) than originally published. These animals were backcrossed 4 times to NOD/LtJ (JR1976) prior to making the stock homozygous for a smaller C57BL/6JOrl-derived interval (D6Mit254-D6Mit339) around NK1.1 (62.1 cM) and to eliminate heterozygosity at D3Mit95.

Allele

Symbol: Klrb1c^a
Name: antigen Nk-1.1 allele
MGI accession ID: MGI:2384434
Generation method: Not Applicable
Marker symbol: Klrb1c
Marker name: killer cell lectin-like receptor subfamily B member 1C
Chromosome: 6
Strain of origin: Not Applicable
Molecular note: The allele Nk1^a determines the antigen, designated Nk-1.1, detected by an antibody produced in (BALB/c x C3H)F1 mice against CE lymphoid cells; it occurs in strains CE, C57BL/6, C57BR/cd, C57L, C58, DBA/1, MA/My, NZB, SJL, SM, and B10.D2.

Allele

MGI accession ID: MGI:102142
Marker symbol: D6Mit339
Marker name: DNA Segment, Chr 6, Massachusetts Institute of Technology 339
Chromosome: 6

Allele

MGI accession ID: MGI:100340
Marker symbol: D6Mit254
Marker name: DNA segment, Chr 6, Massachusetts Institute of Technology 254
Chromosome: 6