NOD/ShiLtDvsJ

Stock number: 032455
Product name: NOD
Research areas: Developmental Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

This NOD subline, which separated from NOD/ShiLtJ (Stock No. 001976) in 1992, and was then transferred to the public Repository at JAX in 2018, has the same diabetes phenotype as NOD/ShiLtJ with similar onset. However, in addition to many SNP variants this strain also has an intragenic deletion of Icam2 (Chromosome 11), which results in a null allele. No impact on the diabetes phenotype has been attributed to this loss of Icam2.

Detailed description

The non-obese diabetic (NOD) mouse is a polygenic model for type 1 diabetes that is characterized by insulitis, a leukocytic infiltration of the pancreatic islets. During ~35 years since the original inbred strain was developed in Japan, NOD substrains have been established at different laboratories around the world.

A 100-kb deletion on Chromosome 3 distinguishes NOD/ShiLtJ (Stock No. 001976) and NOD/ShiLtDvs (Stock No. 032455) from three other substrains (NOD/BomTac, NOD/MrkTac, and NOD/ShiJcl), whereas a spontaneous 111-kb deletion in the Icam2 gene on Chromosome 11 is unique to the NOD/ShiLtDvs genome (Icam2^m1Dvs). No impact on the diabetes phenotype has been attributed to this loss of Icam2.

As mutations are fixed to homozygosity by continued inbreeding, significant differences in substrain phenotypes are to be expected. This emphasizes the importance of using embryo freezing methods to minimize genetic drift within substrains and of applying appropriate genetic nomenclature to permit substrain recognition when one is used.

Development

The NOD/ShiLtDvs inbred substrain separated from NOD/ShiLt in 1992, before that strain reached generation F70. It was maintained by sibling inbreeding in the laboratory of Dr. David Serreze and embryos were cryopreserved in 2007 at generation +F39 (distributed from his research colony as Stock No. 005100). NOD/ShiLtDvsJ animals were transferred to, and cryopreserved by the Repository at The Jackson Laboratory in 2018 at generation F79. The 111,160 bp deletion on Chromozome 3 was present in NOD/ShiLt before the separation of this substrain and the spontaneous Icam2^m1Dvs (Chromosome 11) null mutation that is specific to this substrain arose in approximately the year 2000.

Allele

Symbol: Il2^m1
Name: mutation 1
MGI accession ID: MGI:4352594
Generation method: Spontaneous
Marker symbol: Il2
Marker name: interleukin 2
Marker synonyms: IL-2; lymphokine; TCGF
Chromosome: 3
Strain of origin: multiple strains
Molecular note: This hypoactive polymorphism, found in MRL/MpJ, SJL/J, and NOD/ShiLtJ inbred strains, includes a smaller polyglutamine tract predicted to shorten the first alpha helix, which forms part of the IL2 receptor binding site.

Allele

Symbol: Gpr84^del
Name: deletion
MGI accession ID: MGI:5812913
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Gpr84
Marker name: G protein-coupled receptor 84
Marker synonyms: EX33; GPCR4
Chromosome: 15
Strain of origin: multiple strains
Molecular note: This spontaneously arising frameshift deletion is located in exon 2 at position 103308576 bp (NCBI Build 37) and results in a premature stop codon. The mutation is predicted to result in a truncated protein lacking the transmembrane domains 4-7. The inbred strains BDP/J, DBA/1J, DBA/2J, I/LnJ, FVB/NJ, LG/J, MRL/MpJ, NODShi/LtJ, NOR/LtJ, P/J, PL/J, SKHIN/Sprd, SJL/J, SM/J are homozygous for the deletion. The allele is segregating in the outbred stocks ICR and CD-1.

Allele

Symbol: Hc⁰
Name: deficient
MGI accession ID: MGI:3027637
Generation method: Spontaneous
Synonyms: C5-; C5-d; C5-def; C5-deficient; Hc^Hfib2; hc^o
Marker symbol: Hc
Marker name: hemolytic complement
Marker synonyms: C5; C5a; C5b; C5D; CPAMD4; ECLZB; He; Hfib2; RGD1561905
Chromosome: 2
Strain of origin: multiple strains
Molecular note: A 2 base "TA" deletion at positions 62 and 63 of an 83 base pair exon near the 5' end of the gene is found in the following mouse strains: A/HeJ, A/J, AKR/J, DBA/2J, I/LnJ, KK/HlJ, MOLF/EiJ, NZB/B1NJ, RF/J, ST/bJ SWR/J, B10.D2/oSnJ. The consequence of this deletion is the creation of a stop codon starting four bases after the deletion. A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5.
General note:

This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, A/J, AKR/J, DBA/2J, NZB/B1NJ, SWR/J, B10.D2/oSnJ

Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The A/J allele contains a 2 bp deletion resulting in deficient Hc mRNA and protein production and is associated with susceptibility to allergen-induced bronchial hyperresponsiveness. (J:108211)

Allele

Symbol: H2^g7
Name: g7 variant
MGI accession ID: MGI:3579321
Generation method: Not Applicable
Synonyms: H-2^g7; H-2g7
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Marker synonyms: H-2; MHC-II
Chromosome: 17
Strain of origin: Not Applicable
General note: The g7 variant has been observed in the following strains: DBR7, NON.NOD-H2^g7

Allele

Symbol: Cdh23^ahl
Name: age related hearing loss 1
MGI accession ID: MGI:3028349
Generation method: Spontaneous
Synonyms: Cdh23^753A; mdfw
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Marker synonyms: 4930542A03Rik; ahl; bob; CDHR23; mdfw; nmf112; nmf181; nmf252; PITA5; sals; USH1D
Chromosome: 10
Strain of origin: multiple strains
Molecular note: Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G-to-A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870) at the 3' end of exon 7 (in ENSMUST00000073242). This hypomorphic allele changes splice donor site G-GT to A-GT, causing skipping of out-of-frame exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains in the encoded peptide and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.

Allele

Symbol: Icam2^m1Dvs
Name: mutation 1, David V Serreze
MGI accession ID: MGI:6120486
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Icam2
Marker name: intercellular adhesion molecule 2
Marker synonyms: CD102; Icam-2
Chromosome: 11
Strain of origin: NOD/ShiLtDvs
Molecular note: Exome sequencing shows this spontaneous intragenic deletion removes all exons except the last one (ENSMUSE00000374954) and this mutation is believed to have arisen in the NOD/ShiLtDvs inbred substrain in approximately the year 2000.

Allele

Symbol: mt-Tr^m2
Name: mutation 2
MGI accession ID: MGI:3832223
Generation method: Spontaneous
Synonyms: 9A
Marker symbol: mt-Tr
Marker name: mitochondrially encoded tRNA arginine
Marker synonyms: MTTR; tRNA; tRNA-Arg; TrnR tRNA
Chromosome: MT
Strain of origin: various
Molecular note: The adenine repeat in the D stem is polymorphic with 9 adenines in this allele.
General note: This polymorphism is present in ALR/Lt, NOD/ShiLtDvs, and SKH2/J. A variant with 10 adenines is found in A/J, ALS/Lt, NOD/ShiLtJ and NZB/B1NJ.

Allele

Symbol: Del(3)1Lt
Name: deletion, Chr 3, Edward H Leiter 1
MGI accession ID: MGI:6120887
Generation method: Spontaneous
Attributes: Null/Knockout
Synonyms: Del1Lt
Marker symbol: Del(3)1Lt
Marker name: deletion, Chr 3, Edward H Leiter 1
Chromosome: 3
Strain of origin: NOD/ShiLtJ
Molecular note: This spontaneous 111,169 bp deletion spans from Chr 3: 24,170,854 bp to 24,282,022 bp (GRCm38/mm10), and includes several QTL and the gene N-acetylated alpha-linked acidic dipeptidase-like 2