"Agouti NOD": Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells

Jing Chen, Peter C. Reifsnyder, Felix Scheuplein, William H. Schott, Maria Mileikovsky, Sharon Soodeen-Karamath, Andras Nagy, Michael H. Dosch, James Ellis, Friedrich Koch-Nolte, Edward H. Leiter

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Penetrance of the complex of genes predisposing the nonobese diabetic (NOD) mouse to autoimmune diabetes is affected by the maternal environment. NOD.CBALs-Tyr+/Lt is an agouti-pigmented Chromosome 7 congenic stock of NOD/Lt mice produced as a resource for embryo transfer experiments to provide the necessary maternal factors and allow the easy identification of NOD (albino) embryo donor phenotype. CBcNO6/Lt, a recombinant congenic agouti stock already containing approximately 50% NOD genome, was used as the donor source of a wild-type CBA tyrosinase allele. When the incidence of diabetes was assessed after nine generations of backcrossing and one generation of sib-sib mating, significant reduction in diabetes development was observed. No difference in diabetes development was observed in Tyr/Tyrc heterozygotes, showing that protection was recessive. Analysis of diabetes progression in another NOD stock congenic for C57BL/6 alleles on Chromosome 7 linked to the glucose phosphate isomerase (Gpi1b) locus provided no protection, indicating that the diabetes resistance (Idd) gene was distal to 34 cM (D7Mit346). Approximately 5 cM of the distal congenic region overlaps a region from C57L previously associated with protection when homozygous. The delayed onset and reduced frequency of diabetes in the NOD.CBALs-Tyr+/Lt stock is an advantage when females of this stock are used as surrogate mothers in studies involving hysterectomy or embryo transfers. Indeed, a newly developed NOD embryonic stem (ES) cell line injected into NOD.CBALs- Tyr+/Lt blastocysts produced approximately 50% live-born mice, of which approximately 11% were chimeric. Presumably because of high genomic instability, no germline transmission was observed.

Original languageEnglish
Pages (from-to)775-783
Number of pages9
JournalMammalian Genome
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

Cite this

Chen, J., Reifsnyder, P. C., Scheuplein, F., Schott, W. H., Mileikovsky, M., Soodeen-Karamath, S., ... Leiter, E. H. (2005). "Agouti NOD": Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells. Mammalian Genome, 16(10), 775-783. https://doi.org/10.1007/s00335-005-0007-1
Chen, Jing ; Reifsnyder, Peter C. ; Scheuplein, Felix ; Schott, William H. ; Mileikovsky, Maria ; Soodeen-Karamath, Sharon ; Nagy, Andras ; Dosch, Michael H. ; Ellis, James ; Koch-Nolte, Friedrich ; Leiter, Edward H. / "Agouti NOD" : Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells. In: Mammalian Genome. 2005 ; Vol. 16, No. 10. pp. 775-783.
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title = "{"}Agouti NOD{"}: Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells",
abstract = "Penetrance of the complex of genes predisposing the nonobese diabetic (NOD) mouse to autoimmune diabetes is affected by the maternal environment. NOD.CBALs-Tyr+/Lt is an agouti-pigmented Chromosome 7 congenic stock of NOD/Lt mice produced as a resource for embryo transfer experiments to provide the necessary maternal factors and allow the easy identification of NOD (albino) embryo donor phenotype. CBcNO6/Lt, a recombinant congenic agouti stock already containing approximately 50{\%} NOD genome, was used as the donor source of a wild-type CBA tyrosinase allele. When the incidence of diabetes was assessed after nine generations of backcrossing and one generation of sib-sib mating, significant reduction in diabetes development was observed. No difference in diabetes development was observed in Tyr/Tyrc heterozygotes, showing that protection was recessive. Analysis of diabetes progression in another NOD stock congenic for C57BL/6 alleles on Chromosome 7 linked to the glucose phosphate isomerase (Gpi1b) locus provided no protection, indicating that the diabetes resistance (Idd) gene was distal to 34 cM (D7Mit346). Approximately 5 cM of the distal congenic region overlaps a region from C57L previously associated with protection when homozygous. The delayed onset and reduced frequency of diabetes in the NOD.CBALs-Tyr+/Lt stock is an advantage when females of this stock are used as surrogate mothers in studies involving hysterectomy or embryo transfers. Indeed, a newly developed NOD embryonic stem (ES) cell line injected into NOD.CBALs- Tyr+/Lt blastocysts produced approximately 50{\%} live-born mice, of which approximately 11{\%} were chimeric. Presumably because of high genomic instability, no germline transmission was observed.",
author = "Jing Chen and Reifsnyder, {Peter C.} and Felix Scheuplein and Schott, {William H.} and Maria Mileikovsky and Sharon Soodeen-Karamath and Andras Nagy and Dosch, {Michael H.} and James Ellis and Friedrich Koch-Nolte and Leiter, {Edward H.}",
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Chen, J, Reifsnyder, PC, Scheuplein, F, Schott, WH, Mileikovsky, M, Soodeen-Karamath, S, Nagy, A, Dosch, MH, Ellis, J, Koch-Nolte, F & Leiter, EH 2005, '"Agouti NOD": Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells' Mammalian Genome, vol. 16, no. 10, pp. 775-783. https://doi.org/10.1007/s00335-005-0007-1

"Agouti NOD" : Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells. / Chen, Jing; Reifsnyder, Peter C.; Scheuplein, Felix; Schott, William H.; Mileikovsky, Maria; Soodeen-Karamath, Sharon; Nagy, Andras; Dosch, Michael H.; Ellis, James; Koch-Nolte, Friedrich; Leiter, Edward H.

In: Mammalian Genome, Vol. 16, No. 10, 10.2005, p. 775-783.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - Identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells

AU - Chen, Jing

AU - Reifsnyder, Peter C.

AU - Scheuplein, Felix

AU - Schott, William H.

AU - Mileikovsky, Maria

AU - Soodeen-Karamath, Sharon

AU - Nagy, Andras

AU - Dosch, Michael H.

AU - Ellis, James

AU - Koch-Nolte, Friedrich

AU - Leiter, Edward H.

PY - 2005/10

Y1 - 2005/10

N2 - Penetrance of the complex of genes predisposing the nonobese diabetic (NOD) mouse to autoimmune diabetes is affected by the maternal environment. NOD.CBALs-Tyr+/Lt is an agouti-pigmented Chromosome 7 congenic stock of NOD/Lt mice produced as a resource for embryo transfer experiments to provide the necessary maternal factors and allow the easy identification of NOD (albino) embryo donor phenotype. CBcNO6/Lt, a recombinant congenic agouti stock already containing approximately 50% NOD genome, was used as the donor source of a wild-type CBA tyrosinase allele. When the incidence of diabetes was assessed after nine generations of backcrossing and one generation of sib-sib mating, significant reduction in diabetes development was observed. No difference in diabetes development was observed in Tyr/Tyrc heterozygotes, showing that protection was recessive. Analysis of diabetes progression in another NOD stock congenic for C57BL/6 alleles on Chromosome 7 linked to the glucose phosphate isomerase (Gpi1b) locus provided no protection, indicating that the diabetes resistance (Idd) gene was distal to 34 cM (D7Mit346). Approximately 5 cM of the distal congenic region overlaps a region from C57L previously associated with protection when homozygous. The delayed onset and reduced frequency of diabetes in the NOD.CBALs-Tyr+/Lt stock is an advantage when females of this stock are used as surrogate mothers in studies involving hysterectomy or embryo transfers. Indeed, a newly developed NOD embryonic stem (ES) cell line injected into NOD.CBALs- Tyr+/Lt blastocysts produced approximately 50% live-born mice, of which approximately 11% were chimeric. Presumably because of high genomic instability, no germline transmission was observed.

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