Quality control and protocols

Phenotypic quality control

Because environment is a potent modulator of type 1 diabetes (T1D) gene penetrance, we will determine if the reported ability of a stock, and its particular genetic modification, to modulate T1D is retained under full-barrier health status. Incidence studies will be performed to determine frequency and rate of mice of each sex, as well as NOD/LtJ. 

View incidence studies

Because environment is a potent modulator of type 1 diabetes (T1D) gene penetrance, the T1DR will determine if the reported ability of a stock, and the particular genetic modification, to modulate T1D is retained under full barrier health status. Incidence studies will be performed to determine frequency and rate of mice of each sex, as well as NOD/LtJ.

In the past, NOD/LtJ mice in The Jackson Laboratory's production colonies developed diabetes at a 90-100% incidence over 30 weeks of age for females and a 40-60% diabetes incidence over 30-40 weeks of age for males. However, in 2006 the incidence was somewhat attenuated (females 65%, males 35%), very likely reflecting stress associated by campus wide blasting associated with construction and in 2008 the incidence is higher than we normally see (females 90%, males 85%), likely reflecting a room environment where the lights were on 24 hours a day for an undetermined amount of time, most likely several months. We are currently monitoring incidence studies for our colony of NOD/LtJ as well as other T1DR strains in our full barrier, sterile supply, specific-pathogen-free (SPF) facility. These mice are housed in Pressurized Individually Ventilated (PIV) racks in a room dedicated to immuno-compromised stocks with minimal disturbance.

Incidence studies are available for the following strains:

Last Modified: August 1, 2012

Genetic quality control

The genetic quality control data listed below is available in either Adobe pdf or Excel spreadsheet format. Each file is organized sequentially by chromosome and lists the microsatellite markers, their cM position, and allele sizes for NOD, 129, and B6 controls, as well as for the particular stock. In the comment field, the microsatellite markers used to discern each diabetes susceptibility/ resistance marker (Idd) have been noted. Additionally, the location of the gene or genes of interest has been defined by a red background.

Genome scans

For stocks in which a congenic interval, transgene or gene knockout has been introduced from another strain, we conduct genome-wide scans to verify the exclusion of unwanted donor strain material. We analyze on average 8 markers per chromosome, which are spaced approximately 10-20 cM apart and delineate NOD, 129, and C57BL/6 origin in the stock's genome.

Chromosome of interest analysis

For stocks in which a congenic interval, transgene or gene knockout have been introduced from another strain, a series of microsatellite markers will be genotyped to determine the extent of donor strain genome in the flanking regions of the target gene or segment. As most mutations are currently made using embryonic stem (ES) cells from 129 substrains, there are always 129 genes carried over in linkage disequilibrium with the targeted allele. The length of the congenic segment can be in excess of 20 cM, even after 10 back-crosses with selection only for the targeted allele. In certain instances, 129 genes in the congenic interval rather that the targeted gene can be responsible for a reduced diabetes frequency in the congenic stock.

Immunology protocols

Dr. Ed Leiter contributed a chapter to Current Protocols in Immunology (1997) (.pdf) 15.9.1-15.9.23, which we have reproduced here by permission of the editor, John Wiley & Sons, Inc.

Stock specific GQC data

The genetic quality control data listed below is available in either Adobe pdf or Excel spreadsheet format. Each file is organized sequentially by chromosome and lists the microsatelite markers, their cM position, and allele sizes for NOD, 129, and B6 controls, as well as for the particular stock. In the comment field, the microsatelite markers used to discern each diabetes susceptibility/ resistance marker (Idd) have been noted. 

Additionally, the location of the gene or genes of interest has been defined by a red background.The following six stocks have complete Genome Scan, including Idd markers, as well as complete Chromosome of Interest Analyses.

Genome Scans (MIt markers or SNP's)

Common Name STOCK No.
Excel File
Stock No.
pdf File
NOD.Ifng knockout 2575.xls 2575.pdf
NOD.Pfp knockout 3505.xls 3505.pdf
NOD.Il4 knockout 4222.xls 4222.pdf
NOD.Il10 knockout 4266.xls 4266.pdf
NOD.Il4/Il10 dbl knockout 4291.xls 4291.pdf
NOD.Ifngrb knockout 4352.xls 4352.pdf
NOD.B2m Knockout 2309.xls 2309.pdf
NOD.Cd38 knockout 004311.xls 004311.pdf
NOD.Stat4 knockout 004671.xls 004671.pdf
NOD.Cd28 knockout 004761.xls 004761.pdf
NOD.Sell, Itgb7 Knockout 004943.xls 004943.pdf
NOD.Itgb7 Knockout 004944.xls 004944.pdf
NOD.Casp1 Knockout 004947.xls 004947.pdf
NOD.Ins1 Knockout 005035.xls 005035.pdf
NOD.Ins2 Knockout 005036.xls 005036.pdf
NOD.Il1r1 Knockout 005078.xls 005078.pdf
NOD.Ica1 Knockout 005080.xls 005080.pdf
NOD.Cd80, Cd86, Rag1 Knockout 005273.xls 005273.pdf
NOD.Cd38 Knockout 005345.xls 005345.pdf
NOD.129-Ins2 control 005353 pdf
NOD.B2m, C2ta 005356.xls 005356.pdf
NOD.Cd8a Knockout 005513.xls 005513.pdf

NOD.Tg(Ins2), Ins1, Ins2 Knockout

(low expressing transgene)

005524.xls 005524.pdf

NOD.Tg(Ins2), Ins1, Ins2 Knockout

(high expressing transgene)

005525.xls 005525.pdf
NOD.Icam1 Knockout (original) 005983.xls 005983.pdf
NOD.DQ8, Ab0 006021.xls 006021.pdf
NOD.DQ6, Ab0 006023.xls 006023.pdf
NOD.DQ6, Ab0, Rag1 006024.xls 006024.pdf
B6.B2R KO, Akita 006860.xls 006860.pdf
FVB-Ins2Akita 006867.pdf
DBA/2-Ins2Akita 007562.pdf
NOD.Ctsb -/- 008051.pdf
NOD.Cg-MIP-GFP 008173.pdf
NOD.Cstl -/- 008352.pdf
NOD.Foxp3-EGFP/cre 008694.pdf
NOD.H2-Ab1 -/- 010966.pdf

List of Stocks with completed Chromosome of Interest and Idd sweep analysis


Common Name Stock No. pdf or JpgFile
B6.NOD Idd1

3300.pdf

B6.NOD Idd1,4

3068.pdf

B6.NOD Idd1,5

3071.pdf

B6.NOD Idd1,6

3066.pdf

B6.NOD Idd1,3,10

3067.pdf

B6.NOD Idd3,17/10

3059.pdf

B6.NOD Idd4

3065.pdf

B6.NOD Idd5 (c1c line)

3062.pdf

B6.NOD Idd5 (c1t line 2)

3866.pdf

B6.NOD Idd5 (c1t line 3)

3867.pdf

B6.NOD Idd6

3063.pdf

B6.NOD Idd13

3064.pdf

NOD.CD38 KO

4311.jpg

NOD.B2m KO

2309.jpg

NOD.Itgb7, Sell KO 4943.jpg
NOD.Itgb7 KO 4944.jpg
NOD.IL1r1 KO 5078.jpg
NOD.Idd4A 5311.jpg
NOD.Idd4B 5312.jpg
NOD.Idd4C 5313.jpg
NOD.RIP-HA (Tg) 5685.jpg
NOD.RIP-BCL (Tg) 6154.jpg
NOD.HLA-A2.1 5512.jpg
NOD.NOR-Chr.2 2346.jpg
NOD.NOR-Chr.2 3050.jpg
NOD.NOR-Chr.2 3051.jpg
NOD.NOR-CHR.1 5511.jpg
NOD.ABH-Chr18 5073.jpg
NOD.NOR-Chr.4 5510.jpg
B6.NOD-Chr1 and 17 3069.jpg
NOD.CBALS - Hc1 4306.jpg
NOD.Icam1 (original) 5983.jpg
NOD.Ab0, DQ8 6021.jpg
NOD.B6-Gp1 3585.jpg
NOD.BALB-CD45 5616.jpg
CBcNO7A 3052 (CBcNO7 series)
CBcNO7B 3053 (CBcNO7 series)
CBcNO7C 3054 (CBcNO7 series)
CBcNO7D 3055 (CBcNO7 series)
NOD.NOR-Chr. 1 2347 (pdf)
NOD-Leprdb-5J 4939 (pdf)
NOD.129 - Ins1 control 5352 (pdf)
NOD.Tg(Ins2*Y16A) lineB 5522 (pdf)
NOD.Tg(Ins2*Y16A) lineF 5523 (pdf)
NOD.DQ8, Ab0-/-, Rag1-/- 6022 (pdf)
NOD.Tg(Ins2-Cxcl13)1Cys 6154 (pdf)
NOD.Tg(Tcra BDC12-4.1) 6303 (pdf)
NOD.Tg(Tcrb BDC12-4.1) 6304 (pdf)
NOD.Cd1d-/- 6330 (pdf)
NOD.Icam1 -/- 5983 v 6351 (PDF)
NOD.Aire +/- 6360 (pdf)
NOD.HHD 6604 (pdf)
NOD.scid HHD 6605 (pdf)
NOD.IgHEL IgH-/- 6608 (pdf)
NOD.sHEL 6610 (pdf)
NOD.Il4 knockin (NOD.4GET) 6698 (pdf)
NOD. Foxp3sf (scurffy) 6775 (pdf)
NOD.Tg(GFAP-Cd80) 6778 (pdf)
NOD.Vdr 6956.pdf
NOD.B7-1B Tg 7769 (pdf)
NOD.SwR/J-Idd3 7930 (pdf)
NOD.A/J-Idd3 7931 (pdf)
NOD.CAST-Idd3 7932 (pdf)
NOD.CZECH-Idd3 7933(pdf)
NOD.B6-Idd3 7934 (pdf)
NOD.Lc11 (DR3) 8053 (pdf)
NOD.Lc11a (DR3a) 8054 (pdf)
NOD.Lc11b 008055.pdf
NOD.Lc11e (DR3e) 8056 (pdf)
NOD.Lc11f (DR3f) 8057 (pdf)
NOD.Lc11g 008058.pdf
NOD.Lc11i (DR3i) 8059 (pdf)
NOD.Lc11j (DR3j) 8060 (pdf)
NOD.Lc7 8061 (pdf)
NOD.Zc1 8062 (pdf)
NOd.Zc17 8063 (pdf)
NOD.Zc4 8064 (pdf)
NOD.Zc4c 8065 (pdf)
NOD-Ctss -/- 008524.pdf
NOD.Tg(GFAP-B2m), B2m-/- 008542.pdf
NOD.CD11b-DTR 8547 (pdf)
NOD.CD11c-DTR 8549 (pdf)
NOD.B10-Idd5, line 1092 008893.pdf
NOD.B10-Idd5, line 974 008894.pdf

If you have problems downloading this information, please contact the T1DR Project Manager.

Last Modified: February 5, 2010

Genome scans

As an extension of the genome scan, we concentrate on all reported diabetes susceptibility/resistance loci in a separate genomic microsatellite analysis for stocks in which a congenic interval, transgene or gene knockout has been introduced from another strain into NOD (or NOD genome introduced into a diabetes-resistant background). The markers used allow allele distinction between most donor and recipient strains. It should be noted that not all Idd susceptibility alleles are NOD in origin (e.g., Idd7 on Chromosome 7 and Idd14 on Chromosome 13).

Chromosome

Idd

Markers used

1

Idd5

D1Mit18 and D1Mit180

2

Idd13

D2Mit395,  D2Mit17 and D2Mit525

3

Idd3

D3Nds6 and D3Mit95

3

Idd10/17/18

D3Mit95, D3Mit100, and D3Mit345

4

Idd9

D4Mit203

4

Idd11/25

D4Mit203 and D4Mit59

5

Idd15

D5Mit346 and D5Mit48

6

Idd6/19/20

D6Mit31, D6Mit135 and D6Mit198

7

Idd7

D7Mit20 and D7Mit328

9

Idd2

D9Mit25

10

unnamed

D10Mit87

11

Idd4

D11Mit339 and D11Mit298

13

Idd14

D13Mit16 and D13Mit61

14

Idd8

D14Mit110

14

Idd12

D14Mit222

 17

 Idd1/16

D17Mit34

18

Idd21

D18Mit171, D18Mit202, D18Mit208 and D18Mit4

We are always in search of additional markers polymorphic between NOD, 129, and C57BL/6.  If you know of any we do not currently include, please email the T1DR Project Manager with this information.