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General Terms and Conditions

Strain Common Names	NOD.Vdr;      Vdr -/- NOD-;
Genes & Alleles	Vdr;   Vdrtm1Ska;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Background Strain NOD/Leuven Donor Strain (C57BL/6 x CBA)F1 Donating Investigator Chantal Mathieu,   LEGENDO H2 Haplotype g7 Generation N14+N1F1 (09-MAY-08)

Appearance
albino
Related Genotype: A/A Tyr^c/Tyr^c

Strain Description
Heterozygous mice are viable, fertile, and phenotypically indistinguishable from wildtype siblings. Homozygous mutant mice are viable but infertile. No VDR mRNA is detected by RT-PCR in samples from the intestine or kidney or from homozygous mutant embryo. Increased expression of CTP27B1 and reduced expression of CYP24A1 and calbindin-D9k is detected by RT-PCR in samples from VDR-deficient kidneys.

Although mice homozygous for this targeted mutation are viable, shortly after weaning they exhibit dysmorphic features including a flat face and short nose, alopecia, growth retardation, and skeletal defects including hypocalcaemia, decreased bone mineral density, widened growth plates with hypomineralization, less trabeculae and thicker osteo seams. Homozygous mutant mice exhibit metabolic imbalances including abnormally high and low levels of 1,25(OH),2D3 and 25(OH)D3, respectively and abnormal cytokine and chemokine profiles.

Homozygous mice exhibit normal pancreatic islet architecture and insulitis severity is similar to NOD wildtype controls. Diabetes onset and incidence in mutant and wildtype mice is similar for both males (mutants 30% vs wildtypes 38%) and females (mutants 69% versus wildtype 70%) by 250 days of age.

Mice homozygous for this mutation may be useful in studies of rickets, alopecia, skeletal homeostasis, intestinal absorption, the role of 1,25(OH),2D3 in the immune system as it relates to T1D protection, and to determine the function of vitamin D3 analogs in pancreatic beta cells.

Strain Development
Vitamin D receptor, Vdr, is located on Chr 15, 97682461-97736330 bp. Vit. D deficiency in humans increases the risk for type I diabetes in genetically predisposed individuals. In the targeting construct, a neomycin cassette replaced a 1.1-kb fragment containing exon 2, which encodes the first of two zinc fingers in the DNA-binding domain. Properly targeted TT2, (C57BL/6 x CBA)F1, ES cell clones were introduced into CD-1 embryos. Mice carrying this mutation were backcrossed for 14 generation to NOD/Leuven prior to sibling mating. Microsatellite analysis confirms Idd alleles 1 through 15 are NOD in origin. In addition, a concentration of Mit markers were tested on Chr 15 to ensure NOD homozygosity because there are several immune and regulatory genes in close proximity to the Vdr gene. In 2007, the T1DR received this strain at generation N14F7 and mated with NOD/ShiLtJ (Stock No. 001976) once prior to sibling mating.

Mammalian Phenotype Terms assigned by genotype Vdrtm1Ska/Vdrtm1Ska         NOD.Cg-Vdrtm1Ska/CmatJ growth/size phenotype postnatal growth retardation (MGI Ref ID J:127787) mice exhibit growth retardation homeostasis/metabolism phenotype abnormal glucose tolerance (MGI Ref ID J:127787) glucose tolerance is impaired compared to non-NOD mice but the results are identical when compared to NOD mice with wild-type VDR alleles hypocalcemia (MGI Ref ID J:127787) hypocalcemia is found with high levels of the active metabolite of vitamin D in the sera of mice immune system phenotype abnormal T cell number (MGI Ref ID J:127787) there is a significant decrease in the number of double negative (CD4-CD8-) alphabeta T cells found in the spleen compared to littermate controls decreased regulatory T cell number (MGI Ref ID J:127787) there are decreased numbers of CD4+CD25+ T cells found in the spleen, mesenteric lymph nodes and in the thymus abnormal chemokine secretion (MGI Ref ID J:127787) activated macrophages make significantly less CCL2 when activated in vitro with LPS abnormal dendritic cell differentiation (MGI Ref ID J:127787) thymic and lymph node dendritic cells show defective maturation as indicated by low CD86 expression abnormal interleukin-1 secretion (MGI Ref ID J:127787) there is almost a 4-fold reduction in the amount of IL-1 produced by macrophages when activated by LPS in vitro resting macrophages also produce significantly less IL-1 decreased interleukin-6 secretion (MGI Ref ID J:127787) there is a 2-fold reduction in the amount of IL-6 produced by macrophages when activated by LPS in vitro resting macrophages also produce less IL-6 increased susceptibility to autoimmune diabetes (MGI Ref ID J:127787) mice develop insulitis and diabetes at the same rate as NOD mice with wild-type VDR alleles the incidence of diabetes by 250 days of age was 50% in males and 67% in females at N10, and 30% in males and 69% in females at N10 mean onset of disease for male mice is 163 days and for female mice 142 days hematopoietic system phenotype abnormal T cell number (MGI Ref ID J:127787) there is a significant decrease in the number of double negative (CD4-CD8-) alphabeta T cells found in the spleen compared to littermate controls decreased regulatory T cell number (MGI Ref ID J:127787) there are decreased numbers of CD4+CD25+ T cells found in the spleen, mesenteric lymph nodes and in the thymus abnormal dendritic cell differentiation (MGI Ref ID J:127787) thymic and lymph node dendritic cells show defective maturation as indicated by low CD86 expression skeleton phenotype decreased bone density (MGI Ref ID J:127787) decreased bone mineral density is observed along with less trabeculae and thicker osteoid seams increased long bone epiphyseal plate size (MGI Ref ID J:127787) mice have widened growth plates that are hypomineralized skin/coat/nails phenotype alopecia (MGI Ref ID J:127787) mice exhibit alopecia

Gene & Allele Details

Allele Symbol		Vdrtm1Ska
Allele Name		targeted mutation 1, Shigeaki Kato
Common Name(s)		Tokyo VDR-KO; VDR KO; VDR-; VDRKO;
Mutation Made By		Shigeaki Kato,   The University of Tokyo, 113-0032
Strain of Origin		(C57BL/6 x CBA)F1
ES Cell Line Name		TT2
ES Cell Line Strain		(C57BL/6 x CBA)F1
Gene Symbol and Name		Vdr, vitamin D receptor
Chromosome		15
Gene Common Name(s)		NR1I1;
Molecular Note		A neomycin resistance cassette replaced 1.1kb of sequence containing exon 2, which encodes the first zinc finger of the DNA binding domain. RT-PCR and Western blot analysis of intestinal tissue from homozygous mice detected the presence of a truncated transcript and protein that appears to use Met 53 in exon 3 as an initiation site. This truncated protein is able to bind ligand but lacks transactivation activity. [MGI Ref ID J:129684] [MGI Ref ID J:42054]

Control Information

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

Genotyping Protocols

Vdr^tm1Ska

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Vdr

006133

B6.129S4-Vdrtm1Mbd/J

View Strains carrying other alleles of Vdr     (1 strain)

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX12

Research Applications

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

Dermatology Research
Skin and Hair Texture Defects

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) (Congenics with mutations affecting cytokine production by autoreactive T cells)

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Gastrointestinal Defects
Skin Defects

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Growth Factors/Receptors/Cytokines
Immunodeficiency (Inflammatory bowel disease)
Inflammation (Inflammatory bowel disease)

Internal/Organ Research
Kidney Defects

Vdr^tm1Ska related

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Gastrointestinal Defects
Skin Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Immunodeficiency (Inflammatory bowel disease)
Immunodeficiency
Inflammation (Inflammatory bowel disease)

Internal/Organ Research
Gastrointestinal Defects (colitis)

References

Selected Reference(s)

Gysemans C; van Etten E; Overbergh L; Giulietti A; Eelen G; Waer M; Verstuyf A; Bouillon R; Mathieu C. 2007. UNALTERED DIABETES PRESENTATION IN NOD MICE LACKING THE VITAMIN D RECEPTOR. Diabetes :. [PubMed: 17959935]  [MGI Ref ID J:127787]

Yoshizawa T; Handa Y; Uematsu Y; Takeda S; Sekine K; Yoshihara Y ; Kawakami T ; Arioka K ; Sato H ; Uchiyama Y ; Masushige S ; Fukamizu A ; Matsumoto T ; Kato S. 1997. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 16(4):391-6. [PubMed: 9241280]  [MGI Ref ID J:42054]

Additional References

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Price and Supply Information

Strain Name:	NOD.Cg-Vdrtm1Ska/CmatJ
Stock Number:	006956

Price Details

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Supply Details

Standard Supply	Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Type 1 Diabetes Repository collection.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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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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