Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain NOD Donor Strain (129X1/SvJ x 129S1/Sv)F1-Kitl+ H2 Haplotype g7 Generation N20F?+N1F4pN1   Donating Investigator H. Dosch,   University of Toronto

Appearance
pink-eyed, albino
Related Genotype: A/? Tyr^c/Tyr^c

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.

Control Information

	Control
	Wild-type from the colony
	001976 NOD/ShiLtJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ica1

005082

NOD/ShiLt-Tg(ACTB-Ica1/EGFP)18Mdos/MdosJ

View Strains carrying other alleles of Ica1     (1 strain)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ica1tm1Mdos
Allele Name		targeted mutation 1, H Michael Dosch
Allele Type		Targeted (knock-out)
Common Name(s)		ICA69null;
Mutation Made By		H. Dosch,   University of Toronto
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl+
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Ica1, islet cell autoantigen 1
Chromosome		6
Gene Common Name(s)		69kDa; ICA69; ICAp69;
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. [MGI Ref ID J:83526]

Genotyping

Genotyping Information

Genotyping Protocols

Ica1^tm1Mdos, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Winer S; Astsaturov I; Gaedigk R; Hammond-McKibben D; Pilon M; Song A; Kubiak V; Karges W; Arpaia E; McKerlie C; Zucker P; Singh B; Dosch HM. 2002. ICA69(null) nonobese diabetic mice develop diabetes, but resist disease acceleration by cyclophosphamide. J Immunol 168(1):475-82. [PubMed: 11751995]  [MGI Ref ID J:83526]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	Females homozygote for the targeted mutation at The Jackson Laboratory have fertility issues. Recommended breeding scheme is heterozygote x heterozygote or heterozygote female x homozygote male.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Type 1 Diabetes Repository collection.

Control Information

	Control
	Wild-type from the colony
	001976 NOD/ShiLtJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.