Phenotypes Associated with This Genotype

Genotype
MGI:3760616

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: NOD.Cg-Prkdc^scid

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

mortality/aging

premature death ( J:109833 , J:22026 )

• median life span is 37 weeks; death is a result of thymic lymphomas (J:109833)

• average lifespan in SPF housing is 257 days for females and 269 days for males (J:22026)

• the major cause of death is thymic lymphoma (J:22026)

immune system

abnormal thymus lobule morphology ( J:22026 )

• thymic lobes are small and may contain cysts

abnormal thymus corticomedullary boundary morphology ( J:22026 )

• the cortico-medullary junction is not demarcated in tissues from a 10 week old female

increased T cell derived lymphoma incidence ( J:109833 , J:22026 )

• lymphomas metastasize to multiple sites and are the major cause of death (J:22026)

thymus cyst ( J:22026 )

• may be present

increased granulocyte number ( J:22026 )

• Gr1+ splenic and bone marrow granulocytes are increased in comparison to control

decreased lymphocyte cell number ( J:22026 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control, however, percentages of monocytes, neutrophils and eosinophils are increased and total peripheral leukocyte counts are similar

• thymus, spleen and lymph nodes are depleted of lymphoid cells

decreased B cell number ( J:22026 )

• B220+ splenic B cells are decreased (36.0% vs. 10.4%) in comparison to NOD control as measured by flow cytometry

decreased mature B cell number ( J:109833 )

• spleens are deficient in B220+ IgK+ B cells

decreased pre-B cell number ( J:22026 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (30.7% vs. 2.8%)

• B220+ bone marrow pre-B cells are decreased in number (19.0% vs. 10.2%)

decreased NK cell number ( J:22026 )

• no NK1.1+ splenic NK cells were detected by flow cytometry, however some NK cell activity is detected

decreased T cell number ( J:22026 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (44.9% vs. 0.2%)

decreased CD4-positive, alpha-beta T cell number ( J:109833 , J:22026 )

• spleens are deficient in mature T cells (J:109833)

decreased CD8-positive, alpha-beta T cell number ( J:109833 , J:22026 )

• spleens are deficient in mature T cells (J:109833)

increased macrophage cell number ( J:22026 )

• F4/80+ splenic macrophages are increased in comparison to control

spleen hypoplasia ( J:109833 , J:22026 )

• splenic follicles are hypoplastic (J:109833)

• spleen cellularity is decreased four fold in comparison to NOD control (J:22026)

abnormal spleen white pulp morphology ( J:109833 , J:22026 )

• splenic follicles are hypoplastic (J:109833)

• splenic follicles exhibit a marked loss of lymphoid cells, however, red pulp is normal (J:22026)

decreased immunoglobulin level ( J:22026 )

• only 1/11 homozygotes can produce greater than 1 ug/ml serum Ig at up to 100 days of age

• only 2/30 homozygotes can produce greater than 1 ug/ml serum Ig between 100-200 days of age

impaired natural killer cell mediated cytotoxicity ( J:22026 )

• Background Sensitivity: NK cell activity in homozygous spleen cell suspensions is markedly decreased in comparison to homozygotes on the CB17 background

abnormal lymph node morphology ( J:109833 , J:22026 )

• lymph nodes are hypocellular (J:109833)

• lymph nodes lack follicles and consist mostly of stromal cells (J:22026)

decreased level of surface class I molecules ( J:22026 )

impaired complement classical pathway ( J:22026 )

• complement activity is not detected in either homozygous or control sera using a 51Cr-release assay

abnormal response to transplant ( J:109833 , J:22026 )

• mice support CD34+ human stem cell engraftment, although not as well as mice homozygous for Il2rg^tm1Wjl and Prkdc^scid (J:109833)

• human CD45+ cells comprise 5.2% of cells in the spleen, 6.2% in bone marrow, 0.4% in thymus at 10 weeks post-engraftment (J:109833)

• following injection of human T lymphoblastoid cells, 80% of nucleated spleen cells are of human origin by 4 weeks post injection (J:22026)

• peripheral blood has a five fold increase of human cells by 4 weeks post injection (J:22026)

increased length of allograft survival ( J:22026 )

• homozygotes (5-6 weeks of age) do not reject orthotopic tail skin allografts throughout a 3 month observation period

hematopoietic system

abnormal thymus lobule morphology ( J:22026 )

• thymic lobes are small and may contain cysts

abnormal thymus corticomedullary boundary morphology ( J:22026 )

• the cortico-medullary junction is not demarcated in tissues from a 10 week old female

increased T cell derived lymphoma incidence ( J:109833 , J:22026 )

• lymphomas metastasize to multiple sites and are the major cause of death (J:22026)

thymus cyst ( J:22026 )

• may be present

decreased bone marrow cell number ( J:22026 )

• homozygotes have a 40% reduction in nucleated bone marrow cells compared to NOD control

decreased erythrocyte cell number ( J:22026 )

• homozygotes have significantly reduced erythrocyte counts in contrast to NOD control

increased mean corpuscular volume ( J:22026 )

• Background Sensitivity: erythrocyte mean cell volume is elevated in both homozygotes and NOD controls in contrast to homozygotes on the CB17 background

increased granulocyte number ( J:22026 )

• Gr1+ splenic and bone marrow granulocytes are increased in comparison to control

decreased lymphocyte cell number ( J:22026 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control, however, percentages of monocytes, neutrophils and eosinophils are increased and total peripheral leukocyte counts are similar

• thymus, spleen and lymph nodes are depleted of lymphoid cells

decreased B cell number ( J:22026 )

• B220+ splenic B cells are decreased (36.0% vs. 10.4%) in comparison to NOD control as measured by flow cytometry

decreased mature B cell number ( J:109833 )

• spleens are deficient in B220+ IgK+ B cells

decreased pre-B cell number ( J:22026 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (30.7% vs. 2.8%)

• B220+ bone marrow pre-B cells are decreased in number (19.0% vs. 10.2%)

decreased NK cell number ( J:22026 )

• no NK1.1+ splenic NK cells were detected by flow cytometry, however some NK cell activity is detected

decreased T cell number ( J:22026 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (44.9% vs. 0.2%)

decreased CD4-positive, alpha-beta T cell number ( J:109833 , J:22026 )

• spleens are deficient in mature T cells (J:109833)

decreased CD8-positive, alpha-beta T cell number ( J:109833 , J:22026 )

• spleens are deficient in mature T cells (J:109833)

increased macrophage cell number ( J:22026 )

• F4/80+ splenic macrophages are increased in comparison to control

spleen hypoplasia ( J:109833 , J:22026 )

• splenic follicles are hypoplastic (J:109833)

• spleen cellularity is decreased four fold in comparison to NOD control (J:22026)

abnormal spleen white pulp morphology ( J:109833 , J:22026 )

• splenic follicles are hypoplastic (J:109833)

• splenic follicles exhibit a marked loss of lymphoid cells, however, red pulp is normal (J:22026)

decreased immunoglobulin level ( J:22026 )

• only 1/11 homozygotes can produce greater than 1 ug/ml serum Ig at up to 100 days of age

• only 2/30 homozygotes can produce greater than 1 ug/ml serum Ig between 100-200 days of age

impaired natural killer cell mediated cytotoxicity ( J:22026 )

• Background Sensitivity: NK cell activity in homozygous spleen cell suspensions is markedly decreased in comparison to homozygotes on the CB17 background

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:22026 )

N • weekly monitoring of urinary glucose demonstrates that mice do not develop diabetes

N • mice do not develop insulitis in contrast to NOD controls

increased cellular sensitivity to X-ray irradiation induced cell death ( J:109833 )

• mice do not survive doses above 400 cGy

• some irradiated mice exhibit thymic lymphomas or mitotic figures following irradiation

neoplasm

increased T cell derived lymphoma incidence ( J:109833 , J:22026 )

• lymphomas metastasize to multiple sites and are the major cause of death (J:22026)

cellular

increased cellular sensitivity to X-ray irradiation induced cell death ( J:109833 )

• mice do not survive doses above 400 cGy

• some irradiated mice exhibit thymic lymphomas or mitotic figures following irradiation

endocrine/exocrine glands

abnormal thymus lobule morphology ( J:22026 )

• thymic lobes are small and may contain cysts

abnormal thymus corticomedullary boundary morphology ( J:22026 )

• the cortico-medullary junction is not demarcated in tissues from a 10 week old female

increased T cell derived lymphoma incidence ( J:109833 , J:22026 )

• lymphomas metastasize to multiple sites and are the major cause of death (J:22026)

thymus cyst ( J:22026 )

• may be present

growth/size/body

thymus cyst ( J:22026 )

• may be present