Mouse Genome Informatics
hm
    Dclre1ctm2Mcow/Dclre1ctm2Mcow
involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
immune system
• thymus showed absence of the lymphocytic cortex, and predominance of connective tissue with scattered lymphoid cells
• thymus weighted approximately 20% of wildtype and was poorly developed at 2 and 4-5 weeks of age
• lymphoid depletion
• thymoctye counts were 0.7-4% of that observed in wildtype
• arrest of B cell development at an early progenitor stage
• more than 90% of thymocytes were arrested at the CD4-CD8- stage, compared to 5-10% arrested in wildtype, there were at least 20 times more CD4-CD8-CD25+ cells and showed near absence of CD8+CD3+ and CD4+CD3+ mature single-positive cells in 2 week old mutants
• spleen was smaller and poorly developed at 2 and 4-5 weeks of age
• spleens showed reduction in fully developed lymphoid follicles, in which majority of lymphoid cells showed larger nuclei with less dense chromatin and prominent nucleoli
• impaired coding joint rearrangement (10 fold decrease in DH-JH2 and 100 fold decrease in VH7183-JH2 rearrangement and 10-100 fold reduction in TCRbeta and Ddelta2-Jdelta1 coding joint formation) while retaining intact signal ends and close to normal signal joint formation
• B cell proliferation to LPS was 13.5% of that in wildtype
• T cell proliferation to Con A and anti-CD3 was reduced to 16.5 and 18.7% of that seen in wildtype
• lymph nodes were severely depleted of mature lymphocytes, with complete absence of lymphoid follicles
• lymph nodes were smaller and poorly developed at 2 and 4-5 weeks of age

hematopoietic system
• thymus showed absence of the lymphocytic cortex, and predominance of connective tissue with scattered lymphoid cells
• thymus weighted approximately 20% of wildtype and was poorly developed at 2 and 4-5 weeks of age
• lymphoid depletion
• thymoctye counts were 0.7-4% of that observed in wildtype
• arrest of B cell development at an early progenitor stage
• more than 90% of thymocytes were arrested at the CD4-CD8- stage, compared to 5-10% arrested in wildtype, there were at least 20 times more CD4-CD8-CD25+ cells and showed near absence of CD8+CD3+ and CD4+CD3+ mature single-positive cells in 2 week old mutants
• spleen was smaller and poorly developed at 2 and 4-5 weeks of age
• spleens showed reduction in fully developed lymphoid follicles, in which majority of lymphoid cells showed larger nuclei with less dense chromatin and prominent nucleoli
• impaired coding joint rearrangement (10 fold decrease in DH-JH2 and 100 fold decrease in VH7183-JH2 rearrangement and 10-100 fold reduction in TCRbeta and Ddelta2-Jdelta1 coding joint formation) while retaining intact signal ends and close to normal signal joint formation
• B cell proliferation to LPS was 13.5% of that in wildtype
• T cell proliferation to Con A and anti-CD3 was reduced to 16.5 and 18.7% of that seen in wildtype

cellular
• coding joint formation was undetectable in MEFs in an extrachromosomal V(D)J recombination assay
• MEFs exhibit elevated sensitivity to ionizing radiation

endocrine/exocrine glands
• thymus showed absence of the lymphocytic cortex, and predominance of connective tissue with scattered lymphoid cells
• thymus weighted approximately 20% of wildtype and was poorly developed at 2 and 4-5 weeks of age
• thymoctye counts were 0.7-4% of that observed in wildtype

Mouse Models of Human Disease
OMIM IDRef(s)
Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation 602450 J:96535