Phenotypes Associated with This Genotype

Genotype
MGI:3760369

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: C.BKa-Prkdc^scid

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

mortality/aging

premature death ( J:6958 )

• lifespan is shortened in conventional housing, however, in an SPF environment homozygotes can live to more than one year

immune system

immune system phenotype ( J:22026 )

N • in contrast to homozygotes on the NOD background, spleen cell suspensions from homozygous CB17 mice exhibit NK cell activity

decreased B cell proliferation ( J:6958 )

• spleen cells do not proliferate in response to LPS

decreased T cell proliferation ( J:6958 )

• splenic T cells do not proliferate in response to concanavalin A or to a one-way mixed lymphocyte reaction

salivary gland inflammation ( J:21965 )

• in mice injected i.p. with cells from submandibular gland tissue of diseased Fas^lpr mice, inflammatory lesions are observed in salivary and lacrimal glands

• infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

• mice injected with cells pretreated with anti-CD4 or anti-Vbeta8 do not develop inflammatory lesions or only minor lesions are seen in parotid, submandibular, sublingual and lacrimal glands in majority of transplanted mice

abnormal thymus morphology ( J:6958 )

• the remaining thymocytes that express the Thy1 marker are larger than normal thymocytes

absent thymus cortex ( J:6958 )

• lymphocytic cortex is not evident in thymus

small thymus ( J:6958 )

• 1/10th to 1/100th normal size

increased T cell derived lymphoma incidence ( J:6958 )

• spontaneous T cell lymphomas are found in greater than 10% of homozygotes at 5-9 months of age

• tumors arise in the thymus and are highly invasive and are transplantable

thymus cyst ( J:6958 )

• mucinous cysts are occasionally found

decreased leukocyte cell number ( J:6958 )

• homozygotes are leukopenic

absent B cells ( J:6958 )

• B cells cannot be detected in the spleen with Ig or Lyb-8 (Cd22) markers

absent pre-B cells ( J:6958 )

• pre-B cells cannot be detected in the bone marrow

abnormal spleen white pulp morphology ( J:6958 )

• splenic follicles are devoid of lymphocytic cells

absent Peyer's patches ( J:6958 )

• Peyers patches are rarely visible

lymph node hypoplasia ( J:6958 )

• lymph nodes have only a few lymphoid cells, however, sinuses are well-formed and contain macrophages

small lymphoid organs ( J:6958 )

lymphoid hypoplasia ( J:6958 )

• lymphid organs are 1/10th or less of normal size

• lymph organs consist mostly of supportive tissue with varying numbers of fibroblasts, macrophages and histiocytes

abnormal humoral immune response ( J:6958 )

• mice are unable to produce specific antibody to two T-independent antigens

decreased immunoglobulin level ( J:6958 , J:22026 )

• 31/206 mice tested have low levels of serum immunoglobulin, all 31 have an IgG isotype and of these, 17 also have an IgM isotype (J:6958)

• the remaining 175/206 mice do not have detectable serum immunoglobulin (J:6958)

• only 1/11 homozygotescan produce greater than 1 ug/ml serum Ig at up to 100 days of age, however, 21/29 homozygotes produce greater than 1 ug/ml between 100-200 days of age (J:22026)

decreased IgG level ( J:6958 )

• hypogammaglobulinemic

abnormal response to transplant ( J:22026 )

• following injection of human T lymphoblastoid cells, 40% of nucleated spleen cells are of human origin by 4 weeks post injection

increased length of allograft survival ( J:6958 , J:22026 )

• homozygotes do not reject full thickness skin allografts (J:6958)

• 1/5 homozygotes (5-6 weeks of age) reject orthotopic tail skin allografts throughout a 3 month observation period (J:22026)

hematopoietic system

hematopoietic system phenotype ( J:22026 )

N • in contrast to homozygotes on the NOD background, homozygous CB17 mice exhibit normal erythrocyte mean cell volumes

decreased B cell proliferation ( J:6958 )

• spleen cells do not proliferate in response to LPS

decreased T cell proliferation ( J:6958 )

• splenic T cells do not proliferate in response to concanavalin A or to a one-way mixed lymphocyte reaction

abnormal thymus morphology ( J:6958 )

• the remaining thymocytes that express the Thy1 marker are larger than normal thymocytes

absent thymus cortex ( J:6958 )

• lymphocytic cortex is not evident in thymus

small thymus ( J:6958 )

• 1/10th to 1/100th normal size

increased T cell derived lymphoma incidence ( J:6958 )

• spontaneous T cell lymphomas are found in greater than 10% of homozygotes at 5-9 months of age

• tumors arise in the thymus and are highly invasive and are transplantable

thymus cyst ( J:6958 )

• mucinous cysts are occasionally found

decreased leukocyte cell number ( J:6958 )

• homozygotes are leukopenic

absent B cells ( J:6958 )

• B cells cannot be detected in the spleen with Ig or Lyb-8 (Cd22) markers

absent pre-B cells ( J:6958 )

• pre-B cells cannot be detected in the bone marrow

abnormal spleen white pulp morphology ( J:6958 )

• splenic follicles are devoid of lymphocytic cells

decreased immunoglobulin level ( J:6958 , J:22026 )

• 31/206 mice tested have low levels of serum immunoglobulin, all 31 have an IgG isotype and of these, 17 also have an IgM isotype (J:6958)

• the remaining 175/206 mice do not have detectable serum immunoglobulin (J:6958)

• only 1/11 homozygotescan produce greater than 1 ug/ml serum Ig at up to 100 days of age, however, 21/29 homozygotes produce greater than 1 ug/ml between 100-200 days of age (J:22026)

decreased IgG level ( J:6958 )

• hypogammaglobulinemic

neoplasm

increased T cell derived lymphoma incidence ( J:6958 )

• spontaneous T cell lymphomas are found in greater than 10% of homozygotes at 5-9 months of age

• tumors arise in the thymus and are highly invasive and are transplantable

digestive/alimentary system

salivary gland inflammation ( J:21965 )

• in mice injected i.p. with cells from submandibular gland tissue of diseased Fas^lpr mice, inflammatory lesions are observed in salivary and lacrimal glands

• infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

• mice injected with cells pretreated with anti-CD4 or anti-Vbeta8 do not develop inflammatory lesions or only minor lesions are seen in parotid, submandibular, sublingual and lacrimal glands in majority of transplanted mice

endocrine/exocrine glands

salivary gland inflammation ( J:21965 )

• in mice injected i.p. with cells from submandibular gland tissue of diseased Fas^lpr mice, inflammatory lesions are observed in salivary and lacrimal glands

• infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

• mice injected with cells pretreated with anti-CD4 or anti-Vbeta8 do not develop inflammatory lesions or only minor lesions are seen in parotid, submandibular, sublingual and lacrimal glands in majority of transplanted mice

abnormal thymus morphology ( J:6958 )

• the remaining thymocytes that express the Thy1 marker are larger than normal thymocytes

absent thymus cortex ( J:6958 )

• lymphocytic cortex is not evident in thymus

small thymus ( J:6958 )

• 1/10th to 1/100th normal size

increased T cell derived lymphoma incidence ( J:6958 )

• spontaneous T cell lymphomas are found in greater than 10% of homozygotes at 5-9 months of age

• tumors arise in the thymus and are highly invasive and are transplantable

thymus cyst ( J:6958 )

• mucinous cysts are occasionally found

growth/size/body

thymus cyst ( J:6958 )

• mucinous cysts are occasionally found

cellular

decreased B cell proliferation ( J:6958 )

• spleen cells do not proliferate in response to LPS

decreased T cell proliferation ( J:6958 )

• splenic T cells do not proliferate in response to concanavalin A or to a one-way mixed lymphocyte reaction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, Nk cell-positive		DOID:0090013	OMIM:601457	J:6958