Phenotypes Associated with This Genotype

Genotype
MGI:3790970

• Allelic Composition: Vdr^tm1Ska/Vdr^tm1Ska
• Genetic Background: NOD.Cg-Vdr^tm1Ska/CmatJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

postnatal growth retardation ( J:127787 )

• mice exhibit growth retardation

homeostasis/metabolism

decreased circulating calcium level ( J:127787 )

• hypocalcemia is found with high levels of the active metabolite of vitamin D in the sera of mice

abnormal glucose tolerance ( 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

immune system

abnormal dendritic cell differentiation ( J:127787 )

• thymic and lymph node dendritic cells show defective maturation as indicated by low CD86 expression

abnormal T cell number ( 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 ( 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 ( J:127787 )

• activated macrophages make significantly less CCL2 when activated in vitro with LPS

abnormal interleukin-1 secretion ( 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 ( 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 ( 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

abnormal dendritic cell differentiation ( J:127787 )

• thymic and lymph node dendritic cells show defective maturation as indicated by low CD86 expression

abnormal T cell number ( 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 ( J:127787 )

• there are decreased numbers of CD4⁺CD25⁺ T cells found in the spleen, mesenteric lymph nodes and in the thymus

skeleton

increased long bone epiphyseal plate size ( J:127787 )

• mice have widened growth plates that are hypomineralized

decreased bone mineral density ( J:127787 )

• decreased bone mineral density is observed along with less trabeculae and thicker osteoid seams

integument

alopecia ( J:127787 )

• mice exhibit alopecia

cellular

abnormal dendritic cell differentiation ( J:127787 )

• thymic and lymph node dendritic cells show defective maturation as indicated by low CD86 expression