Phenotypes associated with this allele

• Allele Symbol: Prkdc^scid
• Allele Name: severe combined immunodeficiency
• Allele ID: MGI:1857113
• Summary: 39 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkdc^scid/Prkdc^scid	B6.Cg-Prkdc^scid/Sz	MGI:3760627
hm2	Prkdc^scid/Prkdc^scid	C.BKa-Prkdc^scid	MGI:3760369
hm3	Prkdc^scid/Prkdc^scid	involves: BALB/c * C57BL/10ScSn * C57BL/Ka	MGI:5490614
hm4	Prkdc^scid/Prkdc^scid	involves: BALB/c * C57BL/6 * C57BL/Ka	MGI:4839069
hm5	Prkdc^scid/Prkdc^scid	involves: BALB/c * C57BL/Ka	MGI:3767421
hm6	Prkdc^scid/Prkdc^scid	NOD.Cg-Prkdc^scid	MGI:3760616
hm7	Prkdc^scid/Prkdc^scid	NOD.Cg-Prkdc^scid/J	MGI:3844695
cx8	Lyst^bg-J/Lyst^bg-J Prkdc^scid/Prkdc^scid	B6.Cg-Lyst^bg-J Prkdc^scid/Sz	MGI:3760873
cx9	Prkdc^scid/Prkdc^scid Tg(CSF2)2Ygy/0 Tg(IL3)1Ygy/0	CB17.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy	MGI:3620239
cx10	Prkdc^scid/Prkdc^scid Tg(CSF2)2Ygy/0 Tg(IL3)1Ygy/0 Tg(KITLG)3Ygy/0	CB17.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy Tg(KITLG)3Ygy	MGI:3620237
cx11	Prkdc^scid/Prkdc^scid Tg(INS-HBEGF*L148S*P149T)70Rin/0	C.BKa-Prkdc^scid Tg(INS-HBEGF*L148S*P149T)70Rin	MGI:5565224
cx12	Prkdc^scid/Prkdc^scid Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129 * C3H * CF-1	MGI:4361478
cx13	Igh^tm2Cgn/Igh^+ Igk^tm2Rsky/Igk^+ Prkdc^scid/Prkdc^scid	involves: 129P2/OlaHsd * BALB/c * C57BL/Ka	MGI:3851176
cx14	Prkdc^scid/Prkdc^scid Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6J	MGI:4456092
cx15	Prkdc^scid/Prkdc^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6J	MGI:2665138
cx16	Prkdc^scid/Prkdc^scid Rasa3^scat/Rasa3^scat	involves: BALB/c * BALB/cBy * C57BL	MGI:5433361
cx17	Dmd^mdx/Dmd^mdx Prkdc^scid/Prkdc^scid	involves: BALB/c * C57BL/10ScSn * C57BL/Ka	MGI:5490611
cx18	Prkdc^scid/Prkdc^scid Tg(Tcrb)93Vbo/0	involves: Balb/c * C57BL/Ka * C57BL/Lia * CBA/BrA	MGI:3839250
cx19	Prkdc^scid/Prkdc^scid Sst1^C57BL/6J/Sst1^C57BL/6J	involves: C3HeB/FeJ * C57BL/6J	MGI:3700127
cx20	Prkdc^scid/Prkdc^+ Tg(LPV-TAg1135)11Tvd/0	involves: C57BL/6J * DBA/2J	MGI:2665137
cx21	Prkdc^scid/Prkdc^scid Tg(LPV-TAg1135)11Tvd/0	involves: C57BL/6J * DBA/2J	MGI:2665136
cx22	B2m^tm1Unc/B2m^tm1Unc Emv30^b/Emv30^b Prkdc^scid/Prkdc^scid Tg(B2M)55Hpl/? Mcph1^Tg(HLA-A2.1)1Enge/?	NOD.Cg-B2m^tm1Unc Mcph1^Tg(HLA-A2.1)1Enge Emv30^b Prkdc^scid Tg(B2M)55Hpl/Dvs	MGI:5707036
cx23	B2m^tm1Unc/B2m^tm1Unc Prkdc^scid/Prkdc^scid	NOD.Cg-B2m^tm1Unc Prkdc^scid	MGI:3607137
cx24	Emv30^b/Emv30^b Prkdc^scid/Prkdc^scid	NOD.Cg-Emv30^b Prkdc^scid/Dvs	MGI:3796629
cx25	Emv30^b/Emv30^b Prkdc^scid/Prkdc^scid Tg(IghH280)48Dvs/? Tg(IgkH280)934Dvs/?	NOD.Cg-Emv30^b Prkdc^scid Tg(IghH280)48Dvs Tg(IgkH280)934Dvs/Dvs	MGI:6303746
cx26	Prkdc^scid/Prkdc^scid Tg(TcrLCMV)327Sdz/?	NOD.Cg-Emv30^b Prkdc^scid Tg(TcrLCMV)327Sdz/DvsJ	MGI:3810167
cx27	Prkdc^scid/Prkdc^scid Mcph1^Tg(HLA-A2.1)1Enge/Mcph1^+	NOD.Cg-Mcph1^Tg(HLA-A2.1)1Enge Prkdc^scid/Dvs	MGI:3845377
cx28	Prkdc^scid/Prkdc^scid Tg(B2M)55Hpl/0 Mcph1^Tg(HLA-A2.1)1Enge/Mcph1^+	NOD.Cg-Mcph1^Tg(HLA-A2.1)1Enge Prkdc^scid Tg(B2M)55Hpl/Sz	MGI:3844698
cx29	Prkdc^scid/Prkdc^scid Idua^tm1Clk/Idua^+	NOD.Cg-Prkdc^scid Idua^tm1Clk/J	MGI:3580455
cx30	Prkdc^scid/Prkdc^scid Idua^tm1Clk/Idua^tm1Clk	NOD.Cg-Prkdc^scid Idua^tm1Clk/J	MGI:3580456
cx31	Il2rg^tm1Wjl/Y Prkdc^scid/Prkdc^scid	NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/Sz	MGI:3770662
cx32	Il2rg^tm1Wjl/Il2rg^tm1Wjl Prkdc^scid/Prkdc^scid	NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/Sz	MGI:3770657
cx33	Prkdc^scid/Prkdc^scid Tg(CSF2)2Ygy/0 Tg(IL3)1Ygy/0 Tg(KITLG)3Ygy/0	NOD.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy Tg(KITLG)3Ygy	MGI:3620462
cx34	Prkdc^scid/Prkdc^scid Tg(Ins2-Fasl)24Ach/0	NOD.Cg-Prkdc^scid Tg(Ins2-Fasl)24Ach	MGI:3663017
cx35	Prkdc^scid/Prkdc^scid Tg(INS-Il10)#Sar/0	NOD.Cg-Prkdc^scid Tg(INS-Il10)#Sar	MGI:3622780
cx36	Prkdc^scid/Prkdc^scid Tg(TcraAI4)1Dvs/0 Tg(TcrbAI4)1Dvs/0	NOD.Cg-Prkdc^scid Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs	MGI:3618702
cx37	Prkdc^scid/Prkdc^scid Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz/Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz	NOD.Cg-Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz Prkdc^scid/Gck	MGI:3809476
cx38	Lyst^bg/Lyst^bg Prkdc^scid/Prkdc^scid	Not Specified	MGI:3848455
cx39	Prkdc^scid/Prkdc^scid Gnrh1^hpg/Gnrh1^hpg	STOCK Prkdc^scid Gnrh1^hpg/Bm	MGI:3581148

Genotype
MGI:3760627

hm1

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: B6.Cg-Prkdc^scid/Sz

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

immune system

stomach inflammation ( J:120556 )

• 5 weeks after Helicobacter pylori infection, mice have a significantly decreased gastritis inflammation score compared to infected wild-type mice

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

increased granulocyte number ( J:34814 )

• Gr1+ splenic and bone marrow granulocytes are increased by 4 fold in comparison to control in 10-14 week old mice and continue increasing with age

increased eosinophil cell number ( J:34814 )

increased neutrophil cell number ( J:34814 )

increased NK cell number ( J:34814 )

• NK1.1+ splenic cells are increased by 8 fold in comparison to control in 10-14 week old mice, however, numbers are reduced in 10-12 month old mice

decreased lymphocyte cell number ( J:34814 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control

decreased B cell number ( J:34814 )

• B220+ splenic B cells are decreased (53.0.0% vs. 4.7%) in comparison to C57BL/6 control in 10-14 week old mice

decreased pre-B cell number ( J:34814 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (40.0% vs. 0.9%) in 10-14 week old mice

decreased T cell number ( J:34814 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (37.1% vs. <0.1%) in 10-14 week old mice

decreased CD4-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD4+ cells are not CD3+CD4+

decreased CD8-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD8+ cells are not CD3+CD8+

increased macrophage cell number ( J:34814 )

• F4/80+ splenic macrophages are increased by almost 7 fold in comparison to control in 10-14 week old mice, however numbers are reduced in 10-12 month old mice

increased monocyte cell number ( J:34814 )

spleen hypoplasia ( J:34814 )

• homozygotes have four fold reduction in spleen cellularity at 10-14 weeks old as compared to controls

• mice aged to 10-12 months have some increase in cellularity, but it remains less than half that of control mice

abnormal spleen white pulp morphology ( J:34814 )

• follicles are absent

decreased immunoglobulin level ( J:34814 )

• only 2/10 homozygotes produce greater than 1 ug/ml serum Ig between 1-29 weeks of age, however, between 30-57 weeks of age all mice produce greater than 1 ug/ml (ranging from 2-30 ug/ml)

abnormal NK cell physiology ( J:34814 )

• NK cell activity is markedly elevated in comparison to control

abnormal Peyer's patch morphology ( J:34814 )

• patches contain few lymphoid cells

small Peyer's patches ( J:34814 )

abnormal lymph node B cell domain morphology ( J:34814 )

• follicles are absent

abnormal level of surface class II molecules ( J:34814 )

• class II expression is reduced 4 fold on spleen cells in 10-14 week old mice

abnormal complement pathway ( J:22026 , J:34814 )

• homozygotes exhibit elevated levels of complement activity in comparison to control (J:22026)

hematopoietic system

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

increased granulocyte number ( J:34814 )

• Gr1+ splenic and bone marrow granulocytes are increased by 4 fold in comparison to control in 10-14 week old mice and continue increasing with age

increased eosinophil cell number ( J:34814 )

increased neutrophil cell number ( J:34814 )

increased NK cell number ( J:34814 )

• NK1.1+ splenic cells are increased by 8 fold in comparison to control in 10-14 week old mice, however, numbers are reduced in 10-12 month old mice

decreased lymphocyte cell number ( J:34814 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control

decreased B cell number ( J:34814 )

• B220+ splenic B cells are decreased (53.0.0% vs. 4.7%) in comparison to C57BL/6 control in 10-14 week old mice

decreased pre-B cell number ( J:34814 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (40.0% vs. 0.9%) in 10-14 week old mice

decreased T cell number ( J:34814 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (37.1% vs. <0.1%) in 10-14 week old mice

decreased CD4-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD4+ cells are not CD3+CD4+

decreased CD8-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD8+ cells are not CD3+CD8+

increased macrophage cell number ( J:34814 )

• F4/80+ splenic macrophages are increased by almost 7 fold in comparison to control in 10-14 week old mice, however numbers are reduced in 10-12 month old mice

increased monocyte cell number ( J:34814 )

spleen hypoplasia ( J:34814 )

• homozygotes have four fold reduction in spleen cellularity at 10-14 weeks old as compared to controls

• mice aged to 10-12 months have some increase in cellularity, but it remains less than half that of control mice

abnormal spleen white pulp morphology ( J:34814 )

• follicles are absent

decreased immunoglobulin level ( J:34814 )

• only 2/10 homozygotes produce greater than 1 ug/ml serum Ig between 1-29 weeks of age, however, between 30-57 weeks of age all mice produce greater than 1 ug/ml (ranging from 2-30 ug/ml)

abnormal NK cell physiology ( J:34814 )

• NK cell activity is markedly elevated in comparison to control

digestive/alimentary system

stomach inflammation ( J:120556 )

• 5 weeks after Helicobacter pylori infection, mice have a significantly decreased gastritis inflammation score compared to infected wild-type mice

endocrine/exocrine glands

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

growth/size/body

thymus cyst ( J:34814 )

Genotype
MGI:3760369

hm2

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

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

Genotype
MGI:5490614

hm3

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: involves: BALB/c * C57BL/10ScSn * C57BL/Ka

muscle

muscle phenotype ( J:125527 )

N • no degenerating muscle fibers found in 2 and 12 month old mice

N • 1% of muscle fibers exhibit centrally located nuclei

N • mean muscle fiber area is 1497.7 um<2> and coefficient of variance is 31-43

Genotype
MGI:4839069

hm4

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: involves: BALB/c * C57BL/6 * C57BL/Ka

immune system

abnormal NK cell physiology ( J:115033 )

• following recombinant murine IL12 stimulation NK cells are recruited as in wild-type mice but the subsequent rapid drop off seen in wild-type mice does not occur

hematopoietic system

abnormal NK cell physiology ( J:115033 )

• following recombinant murine IL12 stimulation NK cells are recruited as in wild-type mice but the subsequent rapid drop off seen in wild-type mice does not occur

Genotype
MGI:3767421

hm5

• Allelic Composition: Prkdc^scid/Prkdc^scid
• Genetic Background: involves: BALB/c * C57BL/Ka

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:126867 )

• migration of proliferated intestinal epithelial cells (IEC) toward the top of the villi, the number of proliferating IECs, and MHC class II expression on IECs are augmented in mutants compared to wild-type controls

Genotype
MGI:3760616

hm6

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

mortality/aging

premature death ( J:22026 , 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)

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

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:22026 , J:109833 )

• 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:22026 , J:109833 )

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

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

• 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:22026 , J:109833 )

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

• splenic follicles are hypoplastic (J:109833)

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

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

• splenic follicles are hypoplastic (J:109833)

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:22026 , J:109833 )

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

• lymph nodes are hypocellular (J:109833)

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:22026 , 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)

• 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)

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:22026 , J:109833 )

• 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:22026 , J:109833 )

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

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

• 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:22026 , J:109833 )

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

• splenic follicles are hypoplastic (J:109833)

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

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

• splenic follicles are hypoplastic (J:109833)

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

neoplasm

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

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

cellular

increased cellular sensitivity to X-ray irradiation ( 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:22026 , J:109833 )

• 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

Genotype
MGI:3844695

hm7

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

homeostasis/metabolism

increased circulating glucose level ( J:91764 )

• following treatment with streptozotocin, mice exhibit increased glucose serum levels that can be restored to euglycemic levels by engraftment of human islet cells

• following intraperitoneal injection of human peripheral blood mononuclear cells, 11 of 12 streptozotocin-treated mice engrafted with human islet cells exhibit increased glucose serum levels although not as high as pre-transplantation

immune system

abnormal response to transplant ( J:91764 )

• while human islet engrafts in streptozotocin-treated mice appear normal after 4 weeks, subsequent injection of human peripheral blood mononuclear cells results in destructive infiltrate into the human islet graft site, inflammation, loss of engrafted islet beta cells, fibrosis, and necrosis after 3 weeks

• however, this rejection is not due to graft versus host disease

Genotype
MGI:3760873

cx8

• Allelic Composition: Lyst^bg-J/Lyst^bg-J; Prkdc^scid/Prkdc^scid
• Genetic Background: B6.Cg-Lyst^bg-J Prkdc^scid/Sz

immune system

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

abnormal granulocyte morphology ( J:34814 )

• granulocytes are characterized by giant lysosomal sudanophilic granules

increased granulocyte number ( J:34814 )

• Gr1+ splenic and bone marrow granulocytes are increased by almost 9 fold in comparison to control in 10-14 week old mice and continue increasing with age

increased eosinophil cell number ( J:34814 )

abnormal neutrophil morphology ( J:34814 )

• neutrophil lysosomal extracts have decreased elastase activity

increased neutrophil cell number ( J:34814 )

increased NK cell number ( J:34814 )

• NK1.1+ splenic cells are increased by 10 fold in comparison to control in 10-14 week old mice, however, numbers are reduced in 10-12 month old mice

decreased lymphocyte cell number ( J:34814 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control

decreased B cell number ( J:34814 )

• B220+ splenic B cells are decreased (53.0% vs. 5.0%) in comparison to C57BL/6 control in 10-14 week old mice

decreased pre-B cell number ( J:34814 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (40.0% vs. 2.0%) in 10-14 week old mice

decreased T cell number ( J:34814 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (37.1% vs. <0.1%) in 10-14 week old mice

• in 10-12 month old mice, CD3+ cells increase in number (42.4% vs 12.6%)

decreased CD4-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD4+ cells are not CD3+CD4+

decreased CD8-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD8+ cells are not CD3+CD8+ in 10-14 week old mice

• numbers of CD8+ cells increase substantially in 10-12 month old mice (14.1% vs 18.5%), however only half of CD8+ cells are CD3+

increased macrophage cell number ( J:34814 )

• F4/80+ splenic macrophages are increased by 6 fold in comparison to control in 10-14 week old mice, however numbers are reduced in 10-12 month old mice

increased monocyte cell number ( J:34814 )

spleen hypoplasia ( J:34814 )

• homozygotes have five fold reduction in spleen cellularity at 10-14 weeks old as compared to controls

• mice aged to 10-12 months have some increase in cellularity, but it remains less than half that of control mice

abnormal spleen white pulp morphology ( J:34814 )

• follicles are absent

decreased immunoglobulin level ( J:34814 )

• 5/12 mice produce greater than 1 ug/ml serum Ig between 1-29 weeks of age, however, between 30-57 weeks of age all mice produce greater than 1 ug/ml (ranging from 2-30 ug/ml)

impaired natural killer cell mediated cytotoxicity ( J:34814 )

• NK cell activity is markedly decreased in comparison to B6 control, however, it is elevated in comparison to Lyst^bg-J homozygotes

abnormal Peyer's patch morphology ( J:34814 )

• patches contain few lymphoid cells

small Peyer's patches ( J:34814 )

abnormal lymph node morphology ( J:34814 )

• follicles are absent

abnormal level of surface class II molecules ( J:34814 )

• class II expression is reduced 7 fold on spleen cells in 10-14 week old mice

abnormal complement pathway ( J:34814 )

• serum complement activity is markedly elevated in comparison to control

hematopoietic system

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

abnormal granulocyte morphology ( J:34814 )

• granulocytes are characterized by giant lysosomal sudanophilic granules

increased granulocyte number ( J:34814 )

• Gr1+ splenic and bone marrow granulocytes are increased by almost 9 fold in comparison to control in 10-14 week old mice and continue increasing with age

increased eosinophil cell number ( J:34814 )

abnormal neutrophil morphology ( J:34814 )

• neutrophil lysosomal extracts have decreased elastase activity

increased neutrophil cell number ( J:34814 )

increased NK cell number ( J:34814 )

• NK1.1+ splenic cells are increased by 10 fold in comparison to control in 10-14 week old mice, however, numbers are reduced in 10-12 month old mice

decreased lymphocyte cell number ( J:34814 )

• percentages of circulating lymphocytes are significantly decreased in comparison to control

decreased B cell number ( J:34814 )

• B220+ splenic B cells are decreased (53.0% vs. 5.0%) in comparison to C57BL/6 control in 10-14 week old mice

decreased pre-B cell number ( J:34814 )

• there is a significant absence of splenic B cells bearing the Ig kappa light chain (40.0% vs. 2.0%) in 10-14 week old mice

decreased T cell number ( J:34814 )

• significant numbers of CD3+ splenic T cells are absent in comparison to control (37.1% vs. <0.1%) in 10-14 week old mice

• in 10-12 month old mice, CD3+ cells increase in number (42.4% vs 12.6%)

decreased CD4-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD4+ cells are not CD3+CD4+

decreased CD8-positive, alpha-beta T cell number ( J:34814 )

• in addition, existing CD8+ cells are not CD3+CD8+ in 10-14 week old mice

• numbers of CD8+ cells increase substantially in 10-12 month old mice (14.1% vs 18.5%), however only half of CD8+ cells are CD3+

increased macrophage cell number ( J:34814 )

• F4/80+ splenic macrophages are increased by 6 fold in comparison to control in 10-14 week old mice, however numbers are reduced in 10-12 month old mice

increased monocyte cell number ( J:34814 )

spleen hypoplasia ( J:34814 )

• homozygotes have five fold reduction in spleen cellularity at 10-14 weeks old as compared to controls

• mice aged to 10-12 months have some increase in cellularity, but it remains less than half that of control mice

abnormal spleen white pulp morphology ( J:34814 )

• follicles are absent

decreased immunoglobulin level ( J:34814 )

• 5/12 mice produce greater than 1 ug/ml serum Ig between 1-29 weeks of age, however, between 30-57 weeks of age all mice produce greater than 1 ug/ml (ranging from 2-30 ug/ml)

impaired natural killer cell mediated cytotoxicity ( J:34814 )

• NK cell activity is markedly decreased in comparison to B6 control, however, it is elevated in comparison to Lyst^bg-J homozygotes

endocrine/exocrine glands

abnormal thymus morphology ( J:34814 )

• thymus consists of reticular tissues and some cysts

small thymus ( J:34814 )

thymus cyst ( J:34814 )

growth/size/body

thymus cyst ( J:34814 )

Genotype
MGI:3620239

cx9

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(CSF2)2Ygy/0; Tg(IL3)1Ygy/0
• Genetic Background: CB17.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy

immune system

abnormal response to transplant ( J:94302 )

• engraftment of porcine bone marrow cells after bone marrow transplant into irradiated transgenic SCID mice is achieved and porcine hematopoesis is maintained at 7 weeks post-transplant with less efficiency than in mice also expressing the KITLG transgene

Genotype
MGI:3620237

cx10

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(CSF2)2Ygy/0; Tg(IL3)1Ygy/0; Tg(KITLG)3Ygy/0
• Genetic Background: CB17.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy Tg(KITLG)3Ygy

immune system

abnormal response to transplant ( J:94302 , J:106416 )

• at 1 week after transplant of bone marrow cells or PBMC from swine donors in irradiated transgenic SCID recipient mice, the percentage of porcine cells in the WBC in medronate-liposome treated (for depletion of macrophages) recipients is 10x greater than in PBS treated controls (J:94302)

• chimerism in medronate-liposome treated mice at 8 weeks post-transplant is 60% in the marrow compared to less than 30% in PBS treated controls (J:94302)

• engraftment of porcine bone marrow cells after bone marrow transplant into irradiated transgenic SCID mice is achieved and porcine hematopoesis is maintained at 7 weeks post-transplant compared to non transgenic littermates which lose porcine chimerism completely (J:106416)

Genotype
MGI:5565224

cx11

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(INS-HBEGF*L148S*P149T)70Rin/0
• Genetic Background: C.BKa-Prkdc^scid Tg(INS-HBEGF*L148S*P149T)70Rin

homeostasis/metabolism

hyperglycemia ( J:204420 )

• blood glucose is elevated 2 days after administration of diphtheria toxin (DT)

• hyperglycemia is maintained for 65 days after DT administration

• the hyperglycemia of DT treated mice is decreased by insulin injection

• transplantation of wild-type pancreatic islets beneath the renal capsule of DT treated mice brings blood glucose levels to normal

decreased circulating insulin level ( J:204420 )

• plasma insulin levels are decreased 5 days after administration of DT

• following glucose challenge, insulin levels are not increased in DT treated mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:204420 )

• pancreatic islets are irregularly arranged, with alpha and beta cells randomly mixed rather than 80% of beta cells surrounded by 20% of other cells, after administration of DT

decreased pancreatic beta cell number ( J:204420 )

• administration of DT results in a drastic decrease in the number of pancreatic beta cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:204420

Genotype
MGI:4361478

cx12

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129 * C3H * CF-1

cellular

oligozoospermia ( J:129629 )

♂ • 3 of 23 male homozygotes show a significant reduction in total epididymal sperm count (less than 10⁵ sperm) relative to control littermates

♂ • however, remaining homozygotes show only a modest reduction in epididymal sperm count relative to control littermates

abnormal spermatid morphology ( J:129629 )

♂ • 1 of 8 male homozygotes display decreased numbers of elongated spermatids

growth/size/body

decreased body size ( J:129629 )

♂ • male homozygotes are smaller than wild-type and heterozygous control littermates

decreased body weight ( J:129629 )

♂ • between 5 and 10 weeks of age, male homozygotes weigh ~20% less than age-matched control littermates

increased lung weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 50% increase in lung weight relative to body weight

reproductive system

reproductive system phenotype ( J:129629 )

♂N • at 10 weeks of age, male homozygotes show no differences in the wet weight of testis, seminal vesicle or penis relative to body weight; the reproductive tract is intact with morphologically normal penis, seminal vesicles, and testes

small seminiferous tubules ( J:129629 )

♂ • male homozygotes exhibit a small but significant reduction in mean tubule diameter relative to control littermates

♂ • however, no consistent relationship between reduced tubule diameter and quality of spermatogenesis is observed

decreased testes secretion ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 95% reduction in mean intratesticular testosterone levels relative to control littermates

abnormal spermatogenesis ( J:129629 )

♂ • 1 of 8 male homozygotes display a large proportion of tubules containing only spermatogonia or spermatocytes and no mature elongated spermatids; however, the majority (7 of 8) homozygotes display normal spermatogenesis

♂ • reduced sperm count and impaired spermatogenesis is highly correlated with reduced body weight

oligozoospermia ( J:129629 )

♂ • 3 of 23 male homozygotes show a significant reduction in total epididymal sperm count (less than 10⁵ sperm) relative to control littermates

♂ • however, remaining homozygotes show only a modest reduction in epididymal sperm count relative to control littermates

abnormal spermatid morphology ( J:129629 )

♂ • 1 of 8 male homozygotes display decreased numbers of elongated spermatids

male infertility ( J:129629 )

♂ • all adult male homozygotes fail to sire pregnancies in naturally cycling adult B10 females over a 3-week mating trial

♂ • however, epididymal sperm from male homozygotes with a normal sperm count are viable and developmentally competent, as shown by in vitro fertilization of oocytes with development of blastocysts occurring at the expected rate

♂ • exogenous testosterone treatments fail to restore the infertility phenotype as indicated by the absence of vaginal plugs, sperm-positive vaginal smears, or evidence of pseudopregnancy in normal adult females

failure of ejaculation ( J:129629 )

♂ • although male homozygotes display avid interest in females and engage in mounting activity, none of 6 males tested attain ejaculation during the 2-hr test period

♂ • however, erectile reflexes and ejaculation can be induced by electrical stimulation in ~50% of males regardless of genotype

homeostasis/metabolism

decreased circulating testosterone level ( J:129629 )

♂ • at both 6- and 10-weeks of age, male homozygotes show a 78% reduction in mean serum testosterone levels relative to wild-type controls

♂ • at 10 weeks of age, male homozygotes also show a 64% reduction in mean serum androstendione levels relative to control littermates; however, mean serum estradiol levels remain unaffected

♂ • exogenous testosterone treatments of both neonatal and adult male homozygotes result in normal serum testosterone levels but fail to alleviate the infertility phenotype

decreased circulating follicle stimulating hormone level ( J:129629 )

♂ • after 15 min cocaging with a cycling female, adult male homozygotes display significantly lower serum FSH levels than control littermates; however, FSH levels are not as severely reduced as LH leves

decreased circulating luteinizing hormone level ( J:129629 )

♂ • after 15 min cocaging with a cycling female, adult male homozygotes display significantly lower serum LH levels than control littermates

behavior/neurological

failure of copulatory plug deposition ( J:129629 )

♂ • no vaginal plugs or sperm-positive vaginal smears are ever observed in any females housed with homozygous mutant males

abnormal intromission ( J:129629 )

• when introduced to a receptive female, only 2 of 6 male homozygotes proceed to intromission

• in both cases, intromission events are brief and not sustained to ejaculation

• testosterone replacement fails to restore mating competence

decreased mounting behavior ( J:129629 )

♂ • when introduced to a receptive female, all (6 of 6) male homozygotes initially engage in normal anogenital investigation; however, only 4 of 6 display mounting activity

endocrine/exocrine glands

small seminiferous tubules ( J:129629 )

♂ • male homozygotes exhibit a small but significant reduction in mean tubule diameter relative to control littermates

♂ • however, no consistent relationship between reduced tubule diameter and quality of spermatogenesis is observed

decreased testes secretion ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 95% reduction in mean intratesticular testosterone levels relative to control littermates

respiratory system

increased lung weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 50% increase in lung weight relative to body weight

immune system

decreased spleen weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 60% decrease in spleen weight relative to body weight

hematopoietic system

decreased spleen weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 60% decrease in spleen weight relative to body weight

adipose tissue

decreased retroperitoneal fat pad weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 40% decrease in peritoneal fat weight relative to body weight

Genotype
MGI:3851176

cx13

• Allelic Composition: Igh^tm2Cgn/Igh⁺; Igk^tm2Rsky/Igk⁺; Prkdc^scid/Prkdc^scid
• Genetic Background: involves: 129P2/OlaHsd * BALB/c * C57BL/Ka

hematopoietic system

abnormal class switch recombination ( J:150435 )

• B cells show defects in CSR to IgG1 and IgG3 ranging from 30%?70% of controls

immune system

abnormal class switch recombination ( J:150435 )

• B cells show defects in CSR to IgG1 and IgG3 ranging from 30%?70% of controls

Genotype
MGI:4456092

cx14

• Allelic Composition: Prkdc^scid/Prkdc^scid; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die is 214 days

neoplasm

decreased tumor incidence ( J:47667 )

• none of the mutants develop thymomas by 183 days of age

Genotype
MGI:2665138

cx15

• Allelic Composition: Prkdc^scid/Prkdc⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 183 days

neoplasm

increased thymoma incidence ( J:47667 )

• 60% incidence of thymoma

Genotype
MGI:5433361

cx16

• Allelic Composition: Prkdc^scid/Prkdc^scid; Rasa3^scat/Rasa3^scat
• Genetic Background: involves: BALB/c * BALB/cBy * C57BL

hematopoietic system

abnormal hematopoietic system morphology/development ( J:186485 )

• mice exhibit the same phenotype as Rasa3^scat homozygotes

immune system

abnormal immune system morphology ( J:186485 )

• mice exhibit the same phenotype as Rasa3^scat homozygotes

Genotype
MGI:5490611

cx17

• Allelic Composition: Dmd^mdx/Dmd^mdx; Prkdc^scid/Prkdc^scid
• Genetic Background: involves: BALB/c * C57BL/10ScSn * C57BL/Ka

hematopoietic system

decreased B cell number ( J:125527 )

• 9.3% of total blood derived cells express B220+ and no expression of CD19+ cells as determined by cytofluorimetric analysis

absent CD4-positive, alpha-beta T cells ( J:125527 )

• no expression of CD4+ cells as determined by cytofluorimetric analysis

absent CD8-positive, alpha-beta T cells ( J:125527 )

• no expression of CD8+ cells as determined by cytofluorimetric analysis

homeostasis/metabolism

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• higher endurance on treadmill in double mutant than Dmd^mdx mutants

decreased transforming growth factor beta level ( J:125527 )

• costal diaphragm (DIA) has a lower quantity of active TGFB1 in comparison to Dmd^mdx mutant although total quantity is similar

• tibialis anterior (TA) and quadricepts (QA) muscles have a lower quantity of total TGFB1 in comparison to Dmd^mdx mutant

immune system

decreased B cell number ( J:125527 )

• 9.3% of total blood derived cells express B220+ and no expression of CD19+ cells as determined by cytofluorimetric analysis

absent CD4-positive, alpha-beta T cells ( J:125527 )

• no expression of CD4+ cells as determined by cytofluorimetric analysis

absent CD8-positive, alpha-beta T cells ( J:125527 )

• no expression of CD8+ cells as determined by cytofluorimetric analysis

muscle

increased skeletal muscle fiber diameter ( J:125527 )

• area of muscle fibers is 1500-1800 um² and coefficient of variance is 55-65

centrally nucleated skeletal muscle fibers ( J:125527 )

• small, centrally nucleated, regenerating muscle fibers are found in 2 and 12 month old mice

• 46-52% of muscle fibers exhibit centrally located nuclei

skeletal muscle fiber degeneration ( J:125527 )

• degenerating muscle fibers are found in 2 and 12 month old mice

skeletal muscle fibrosis ( J:125527 )

• aged 12 month old double mutant mice exhibit fibrosis, but less than in age-matched Dmd^mdx mice

impaired skeletal muscle contractility ( J:125527 )

• loss of normalized tetanic force in the costal diaphragm (DIA) strips is observed in 2 and 12 month old mice as compared to wild type

• change appears lower in double mutant than in Dmd^mdx mutants

• a similar decrease in normalized tetanic force occurs in the tibialis anterior (TA)

reproductive system

reduced fertility ( J:125527 )

• double mutant mice are less fertile than Dmd^mdx mice

skeleton

abnormal vertebral column morphology ( J:125527 )

• progressive spinal deformity

behavior/neurological

impaired exercise endurance ( J:125527 )

• mice exhibit a shorter time to exhaustion than wild type controls

• higher endurance on treadmill in double mutant than Dmd^mdx mutants

Genotype
MGI:3839250

cx18

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(Tcrb)93Vbo/0
• Genetic Background: involves: Balb/c * C57BL/Ka * C57BL/Lia * CBA/BrA

immune system

abnormal T cell differentiation ( J:111476 )

• thymocytes express high levels of the transgenic TCR-beta chain on their surface that appear to be homodimers

abnormal double-positive T cell morphology ( J:111476 )

• 50% of thymocytes are CD4⁺CD8⁺ compared to scid homozygotes which have no double positive thymocytes

abnormal CD4-positive, alpha beta T cell morphology ( J:111476 )

• T cells are detected in the periphery of these mice compared to the scid homozygotes that lack T cells

• CD4⁺ T cells make up 6.1% of the splenic cells and CD8⁺ make up 0.9% of T cells

abnormal CD8-positive, alpha beta T cell morphology ( J:111476 )

• CD4⁺ T cells make up 6.1% of the splenic cells and CD8⁺ make up 0.9% of T cells

• T cells are detected in the periphery of these mice compared to the scid homozygotes that lack T cells

abnormal single-positive T cell number ( J:111476 )

• small numbers of single-positive thymocytes are in the thymus

• 3% of thymocytes are CD4⁺CD8^- and 7.9% of thymocytes are CD4^-CD8⁺

hematopoietic system

abnormal T cell differentiation ( J:111476 )

• thymocytes express high levels of the transgenic TCR-beta chain on their surface that appear to be homodimers

abnormal double-positive T cell morphology ( J:111476 )

• 50% of thymocytes are CD4⁺CD8⁺ compared to scid homozygotes which have no double positive thymocytes

abnormal CD4-positive, alpha beta T cell morphology ( J:111476 )

• T cells are detected in the periphery of these mice compared to the scid homozygotes that lack T cells

• CD4⁺ T cells make up 6.1% of the splenic cells and CD8⁺ make up 0.9% of T cells

abnormal CD8-positive, alpha beta T cell morphology ( J:111476 )

• T cells are detected in the periphery of these mice compared to the scid homozygotes that lack T cells

• CD4⁺ T cells make up 6.1% of the splenic cells and CD8⁺ make up 0.9% of T cells

abnormal single-positive T cell number ( J:111476 )

• small numbers of single-positive thymocytes are in the thymus

• 3% of thymocytes are CD4⁺CD8^- and 7.9% of thymocytes are CD4^-CD8⁺

Genotype
MGI:3700127

cx19

• Allelic Composition: Prkdc^scid/Prkdc^scid; Sst1^C57BL/6J/Sst1^C57BL/6J
• Genetic Background: involves: C3HeB/FeJ * C57BL/6J

immune system

decreased susceptibility to bacterial infection ( J:93705 )

• resistance to Listeria monocytogenes

• decreased necrotic liver and spleen lesions compared to C3SnSmn.CB17-Prkdc/J

• 500-1000 times less bacterial load compared to C3SnSmn.CB17-Prkdc/J

Genotype
MGI:2665137

cx20

• Allelic Composition: Prkdc^scid/Prkdc⁺; Tg(LPV-TAg1135)11Tvd/0
• Genetic Background: involves: C57BL/6J * DBA/2J

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 183 days

neoplasm

increased thymoma incidence ( J:47667 )

• 93% incidence of thymoma

Genotype
MGI:2665136

cx21

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(LPV-TAg1135)11Tvd/0
• Genetic Background: involves: C57BL/6J * DBA/2J

mortality/aging

premature death ( J:47667 )

• survival time at which half of the mutants are sacrificed or die due to illness is 210 days

neoplasm

increased thymoma incidence ( J:47667 )

• 62% incidence of thymoma, however tumor development is not accelerated compared to heterozygous Prkdc and hemizygous Tg(LPV-TAg1135)11Tvd mice, and is actually slightly delayed

Genotype
MGI:5707036

cx22

• Allelic Composition: B2m^tm1Unc/B2m^tm1Unc; Emv30^b/Emv30^b; Prkdc^scid/Prkdc^scid; Tg(B2M)55Hpl/?; Mcph1^{Tg(HLA-A2.1)1Enge}/?
• Genetic Background: NOD.Cg-B2m^tm1Unc Mcph1^{Tg(HLA-A2.1)1Enge} Emv30^b Prkdc^scid Tg(B2M)55Hpl/Dvs

immune system

decreased susceptibility to autoimmune diabetes ( J:109851 )

• these mice do not develop diabetes and they provide a host in cell transfer studies for assessing HLA-A2.1 selected T cell pathogenicity

Genotype
MGI:3607137

cx23

• Allelic Composition: B2m^tm1Unc/B2m^tm1Unc; Prkdc^scid/Prkdc^scid
• Genetic Background: NOD.Cg-B2m^tm1Unc Prkdc^scid

mortality/aging

premature death ( J:102141 )

• mean life span is 191+11 days

immune system

increased T cell derived lymphoma incidence ( J:102141 )

• associated with shortened lifespan

arrested B cell differentiation ( J:102141 )

• absence of mature B cells in spleen, very little serum Ig

arrested T cell differentiation ( J:102141 )

• few CD4+ and CD8+ cells in spleen and no mature T cells

absent lymphocyte ( J:102141 )

• lacks lymphoid cells in the spleen, lymph nodes and thymus

increased macrophage cell number ( J:102141 )

abnormal NK cell physiology ( J:102141 )

• lacks detectable NK cell activity after pretreatment with NK cell inducer

decreased level of surface class I molecules ( J:102141 )

abnormal response to transplant ( J:102141 )

• mouse supports high levels of human CD4+ T cell engraftment in spleen and peripheral blood following human PBMC injection

• minimal engraftment of human CD19+ B cells (less than 2%) following human PBMC injection

• rapid clearance of human IgG

neoplasm

increased T cell derived lymphoma incidence ( J:102141 )

• associated with shortened lifespan

homeostasis/metabolism

increased liver iron level ( J:102141 )

• intracytoplasmic iron deposition in liver

hematopoietic system

increased T cell derived lymphoma incidence ( J:102141 )

• associated with shortened lifespan

arrested B cell differentiation ( J:102141 )

• absence of mature B cells in spleen, very little serum Ig

arrested T cell differentiation ( J:102141 )

• few CD4+ and CD8+ cells in spleen and no mature T cells

absent lymphocyte ( J:102141 )

• lacks lymphoid cells in the spleen, lymph nodes and thymus

increased macrophage cell number ( J:102141 )

abnormal NK cell physiology ( J:102141 )

• lacks detectable NK cell activity after pretreatment with NK cell inducer

liver/biliary system

increased liver iron level ( J:102141 )

• intracytoplasmic iron deposition in liver

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:102141 )

• associated with shortened lifespan

Genotype
MGI:3796629

cx24

• Allelic Composition: Emv30^b/Emv30^b; Prkdc^scid/Prkdc^scid
• Genetic Background: NOD.Cg-Emv30^b Prkdc^scid/Dvs

neoplasm

increased T cell derived lymphoma incidence ( J:29951 )

• Background Sensitivity: although thymic lymphomas still initiate in the absence of EMV30, their rate of progression is much less than in the presence of the EMV30 allele with the frequency of thymic lymphomas weighing between 170mg and 910mg at 25 weeks of age is only 20.8% compared to 76.2% in EMV30 homozygous controls

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:29951 )

• Background Sensitivity: although thymic lymphomas still initiate in the absence of EMV30, their rate of progression is much less than in the presence of the EMV30 allele with the frequency of thymic lymphomas weighing between 170mg and 910mg at 25 weeks of age is only 20.8% compared to 76.2% in EMV30 homozygous controls

hematopoietic system

increased T cell derived lymphoma incidence ( J:29951 )

• Background Sensitivity: although thymic lymphomas still initiate in the absence of EMV30, their rate of progression is much less than in the presence of the EMV30 allele with the frequency of thymic lymphomas weighing between 170mg and 910mg at 25 weeks of age is only 20.8% compared to 76.2% in EMV30 homozygous controls

immune system

increased T cell derived lymphoma incidence ( J:29951 )

• Background Sensitivity: although thymic lymphomas still initiate in the absence of EMV30, their rate of progression is much less than in the presence of the EMV30 allele with the frequency of thymic lymphomas weighing between 170mg and 910mg at 25 weeks of age is only 20.8% compared to 76.2% in EMV30 homozygous controls

Genotype
MGI:6303746

cx25

• Allelic Composition: Emv30^b/Emv30^b; Prkdc^scid/Prkdc^scid; Tg(IghH280)48Dvs/?; Tg(IgkH280)934Dvs/?
• Genetic Background: NOD.Cg-Emv30^b Prkdc^scid Tg(IghH280)48Dvs Tg(IgkH280)934Dvs/Dvs

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:274578 )

N • mice homozygous for the scid mutation do not develop insulitis despite the NOD background and pro-diabetic transgenes

Genotype
MGI:3810167

cx26

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(TcrLCMV)327Sdz/?
• Genetic Background: NOD.Cg-Emv30^b Prkdc^scid Tg(TcrLCMV)327Sdz/DvsJ

immune system

immune system phenotype ( J:71050 )

N • the presence of the T cell receptor transgene does not increase susceptibility to type 1 diabetes, even in the presence of this transgene NOD mice homozygous for the scid mutation do not develop type 1 diabetes

Genotype
MGI:3845377

cx27

• Allelic Composition: Prkdc^scid/Prkdc^scid; Mcph1^{Tg(HLA-A2.1)1Enge}/Mcph1⁺
• Genetic Background: NOD.Cg-Mcph1^{Tg(HLA-A2.1)1Enge} Prkdc^scid/Dvs

hematopoietic system

abnormal splenocyte morphology ( J:91764 )

• more than 95% of splenocytes express high levels of human HLA-A2.1 protein on their cell surface

immune system

abnormal splenocyte morphology ( J:91764 )

• more than 95% of splenocytes express high levels of human HLA-A2.1 protein on their cell surface

Genotype
MGI:3844698

cx28

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(B2M)55Hpl/0; Mcph1^{Tg(HLA-A2.1)1Enge}/Mcph1⁺
• Genetic Background: NOD.Cg-Mcph1^{Tg(HLA-A2.1)1Enge} Prkdc^scid Tg(B2M)55Hpl/Sz

homeostasis/metabolism

increased circulating glucose level ( J:91764 )

• when islet and HLA-A2 negative human peripheral blood mononuclear cells are transplanted into streptozotocin-treated Rag1^tm1Mom Prf1^tm1Sdz homozygotes serum glucose remains high

• however, when islet and HLA-A2 positive human peripheral blood mononuclear cells are transplanted into streptozotocin-treated Rag1^tm1Mom Prf1^tm1Sdz homozygotes euglycemia is achieved

immune system

abnormal response to transplant ( J:91764 )

• when islet and HLA-A2 negative human peripheral blood mononuclear cells are transplanted into streptozotocin-treated Rag1^tm1Mom Prf1^tm1Sdz homozygotes engrafted islet cells are destroyed

Genotype
MGI:3580455

cx29

• Allelic Composition: Prkdc^scid/Prkdc^scid; Idua^tm1Clk/Idua⁺
• Genetic Background: NOD.Cg-Prkdc^scid Idua^tm1Clk/J

craniofacial

short snout ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

broad head ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

hearing/vestibular/ear

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

vision/eye

enophthalmos ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

integument

rough coat ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

growth/size/body

short snout ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

broad head ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

small ears ( J:139626 )

• this feature distinguishes mice from wild-type controls but is not as severe as observed in homozygotes

Genotype
MGI:3580456

cx30

• Allelic Composition: Prkdc^scid/Prkdc^scid; Idua^tm1Clk/Idua^tm1Clk
• Genetic Background: NOD.Cg-Prkdc^scid Idua^tm1Clk/J

reproductive system

female infertility ( J:139626 )

♀ • matings between homozygote females and heterozygote males are unsuccessful

behavior/neurological

abnormal motor learning ( J:139626 )

• mice trained on a rotating rod have decreased times of latency in subsequent tests compared to controls

• males have more deficient motor learning than females

• for females, there was some improvement in times of latency at all speeds though never to the degree seen for controls

• training failed to improve time of latency for males at the highest speed tested

impaired coordination ( J:139626 )

• mice have decreased times of latency in rotarod tests

• males have worse impairment than females

pup cannibalization ( J:139626 )

♀ • mothers often cannibalize their offspring

craniofacial

abnormal zygomatic bone morphology ( J:139626 )

• mice have thickening of the zygomatic bone

short snout ( J:139626 )

• mice have a short snout that is more evident in females

broad head ( J:139626 )

• mice have broad head that is more evident in females

small ears ( J:139626 )

• mice have small ears that is more evident in females

hearing/vestibular/ear

small ears ( J:139626 )

• mice have small ears that is more evident in females

homeostasis/metabolism

abnormal homeostasis ( J:139626 )

• tissue levels of glycosaminoglycans are extremely high throughout tissues with highest levels in the liver followed by kidney, lung, spleen, heart and brain

increased urine glycosaminoglycan level ( J:139626 )

• urinary excretion of glycosaminoglycans is 6.5-fold higher than in controls

nervous system

abnormal brain morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal brainstem morphology ( J:139626 )

• high ganglioside accumulations are observed

abnormal striatum morphology ( J:139626 )

• high ganglioside accumulations are observed

abnormal hippocampus morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal cerebellum morphology ( J:139626 )

• ganglioside accumulations are observed

abnormal cerebellar cortex morphology ( J:139626 )

• ganglioside accumulations are observed

renal/urinary system

increased urine glycosaminoglycan level ( J:139626 )

• urinary excretion of glycosaminoglycans is 6.5-fold higher than in controls

skeleton

abnormal zygomatic bone morphology ( J:139626 )

• mice have thickening of the zygomatic bone

vision/eye

enophthalmos ( J:139626 )

• mice have a short snout that is more evident in females

integument

rough coat ( J:139626 )

• mice have a rough coat

growth/size/body

short snout ( J:139626 )

• mice have a short snout that is more evident in females

broad head ( J:139626 )

• mice have broad head that is more evident in females

small ears ( J:139626 )

• mice have small ears that is more evident in females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mucopolysaccharidosis I		DOID:12802		J:139626

Genotype
MGI:3770662

cx31

• Allelic Composition: Il2rg^tm1Wjl/Y; Prkdc^scid/Prkdc^scid
• Genetic Background: NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/Sz

mortality/aging

premature death ( J:109833 )

♂ • the majority of autopsies indicate no evidence of lymphomas

♂ • median survival time is lengthened to between 59-95 weeks (median 89 weeks) in contrast to the shorter lifespan observed homozygous Prkdc^scid controls

cellular

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

♂ • mice do not survive doses above or equal to 400cGy

hematopoietic system

abnormal thymus morphology ( J:109833 )

♂ • thymus consists mostly of stromal cells with sporadic cyst structures

decreased mean corpuscular volume ( J:109833 )

♂ • slight decrease in packed cell volume at 10 weeks as compared to to Prkdc^scid controls

decreased leukocyte cell number ( J:109833 )

♂ • decrease in peripheral leukocytes at 10 weeks as compared to to Prkdc^scid controls

decreased immature B cell number ( J:109833 )

♂ • flow cytometric analysis indicates that spleen cells exhibit a reduction in B220+ IgK- immature B cells in comparison to Prkdc^scid controls

decreased mature B cell number ( J:109833 )

♂ • spleens are deficient in B220+ IgK+ B cells

decreased NK cell number ( J:109833 )

♂ • spleen cells from poly(I:C) stimulated 6-8 week old mice exhibit very low levels of NK cell cytotoxic activity

♂ • mice are deficient in cells expressing NK cell markers in comparison to Prkdc^scid controls

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

♂ • spleens are deficient in mature T cells

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

♂ • spleens are deficient in mature T cells

decreased spleen B cell follicle number ( J:109833 )

♂ • spleens do not have detectable follicles

abnormal splenic cell ratio ( J:109833 )

♂ • two fold reduction in nucleated spleen cell numbers in comparison to Prkdc^scid controls

decreased immunoglobulin level ( J:109833 )

♂ • no detectable immunoglobulin in mice at 394-426 days of age

immune system

decreased leukocyte cell number ( J:109833 )

♂ • decrease in peripheral leukocytes at 10 weeks as compared to to Prkdc^scid controls

decreased immature B cell number ( J:109833 )

♂ • flow cytometric analysis indicates that spleen cells exhibit a reduction in B220+ IgK- immature B cells in comparison to Prkdc^scid controls

decreased mature B cell number ( J:109833 )

♂ • spleens are deficient in B220+ IgK+ B cells

decreased NK cell number ( J:109833 )

♂ • spleen cells from poly(I:C) stimulated 6-8 week old mice exhibit very low levels of NK cell cytotoxic activity

♂ • mice are deficient in cells expressing NK cell markers in comparison to Prkdc^scid controls

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

♂ • spleens are deficient in mature T cells

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

♂ • spleens are deficient in mature T cells

decreased immunoglobulin level ( J:109833 )

♂ • no detectable immunoglobulin in mice at 394-426 days of age

abnormal immune system organ morphology ( J:109833 )

♂ • lymph tissues are severely depleted of lymphoid cells

abnormal thymus morphology ( J:109833 )

♂ • thymus consists mostly of stromal cells with sporadic cyst structures

decreased spleen B cell follicle number ( J:109833 )

♂ • spleens do not have detectable follicles

abnormal splenic cell ratio ( J:109833 )

♂ • two fold reduction in nucleated spleen cell numbers in comparison to Prkdc^scid controls

small lymph nodes ( J:109833 )

♂ • lymph nodes in the double mutant are markedly smaller than those of homozygous Prkdc^scid mice

lymph node hypoplasia ( J:109833 )

♂ • lymph nodes are hypocellular

abnormal response to transplant ( J:109833 , J:140388 )

♂ • mice support CD34+ human stem cell engraftment at much higher levels than Prkdc^scid controls (J:109833)

♂ • human CD45+ cells comprise almost 50% of cells in the spleen, approximately 35% in bone marrow and thymus, and 6% in blood at 10 weeks post-engraftment (J:109833)

♂ • irradiated mice engrafted with human hematopoietic stem cells (HSCs) show much greater engraftment of human hematopoietic cells at 12 weeks than control NOD.129S7(B6)-Rag1^tm1Mom homozygotes (J:140388)

♂ • percentages of human CD45+ cells engrafted in bone marrow are higher than in NOD.CB17-Prkdc^scid mice (J:140388)

♂ • levels of human CD45+ cell and CD3+ T cell engraftment are higher in spleens than in NOD.CB17-Prkdc^scid mice (J:140388)

♂ • CD4:CD8 human T cell ratios that are close to normal physiological values and high levels of human B cells are observed in spleens of mice compared to NOD.CB17-Prkdc^scid mice (J:140388)

♂ • engraftment of human lymphohematopoietic cells in blood and thymus, and peripheral blood mononuclear cells (PMBC) engraftment are higher than in NOD.CB17-Prkdc^scid (J:140388)

endocrine/exocrine glands

abnormal thymus morphology ( J:109833 )

♂ • thymus consists mostly of stromal cells with sporadic cyst structures

Genotype
MGI:3770657

cx32

• Allelic Composition: Il2rg^tm1Wjl/Il2rg^tm1Wjl; Prkdc^scid/Prkdc^scid
• Genetic Background: NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/Sz

growth/size/body

thymus cyst ( J:109833 )

♀ • sporadic cyst structures

mortality/aging

premature death ( J:109833 )

♀ • median survival time is lengthened to between 59-95 weeks (median 89 weeks) in contrast to the shorter lifespan observed homozygous Prkdc^scid controls

♀ • the majority of autopsies indicate no evidence of lymphomas

immune system

decreased leukocyte cell number ( J:109833 )

♀ • decrease in peripheral leukocytes at 10 weeks as compared to to Prkdc^scid controls

decreased immature B cell number ( J:109833 )

♀ • flow cytometric analysis indicates that spleen cells exhibit a reduction in B220+ IgK- immature B cells in comparison to Prkdc^scid controls

decreased mature B cell number ( J:109833 )

♀ • spleens are deficient in B220+ IgK+ B cells

decreased NK cell number ( J:109833 )

♀ • mice are deficient in cells expressing NK cell markers in comparison to Prkdc^scid controls

♀ • spleen cells from poly(I:C) stimulated 6-8 week old mice exhibit very low levels of NK cell cytotoxic activity

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

♀ • spleens are deficient in mature T cells

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

♀ • spleens are deficient in mature T cells

decreased immunoglobulin level ( J:109833 )

♀ • no detectable immunoglobulin in mice at 394-426 days of age

abnormal immune system organ morphology ( J:109833 )

♀ • lymph tissues are severely depleted of lymphoid cells

abnormal thymus morphology ( J:109833 )

♀ • thymus consists mostly of stromal cells with sporadic cyst structures

thymus cyst ( J:109833 )

♀ • sporadic cyst structures

decreased spleen B cell follicle number ( J:109833 )

♀ • spleens do not have detectable follicles

abnormal splenic cell ratio ( J:109833 )

♀ • two fold reduction in nucleated spleen cell numbers in comparison to Prkdc^scid controls

small lymph nodes ( J:109833 )

♀ • lymph nodes in the double mutant are markedly smaller than those of homozygous Prkdc^scid mice

lymph node hypoplasia ( J:109833 )

♀ • lymph nodes are hypocellular

abnormal response to transplant ( J:109833 )

♀ • mice support CD34+ human stem cell engraftment at much higher levels than Prkdc^scid controls

♀ • human CD45+ cells comprise almost 50% of cells in the spleen, approximately 35% in bone marrow and thymus, and 6% in blood at 10 weeks post-engraftment

hematopoietic system

abnormal thymus morphology ( J:109833 )

♀ • thymus consists mostly of stromal cells with sporadic cyst structures

thymus cyst ( J:109833 )

♀ • sporadic cyst structures

decreased mean corpuscular volume ( J:109833 )

♀ • slight decrease in packed cell volume at 10 weeks as compared to to Prkdc^scid controls

decreased leukocyte cell number ( J:109833 )

♀ • decrease in peripheral leukocytes at 10 weeks as compared to to Prkdc^scid controls

decreased immature B cell number ( J:109833 )

♀ • flow cytometric analysis indicates that spleen cells exhibit a reduction in B220+ IgK- immature B cells in comparison to Prkdc^scid controls

decreased mature B cell number ( J:109833 )

♀ • spleens are deficient in B220+ IgK+ B cells

decreased NK cell number ( J:109833 )

♀ • mice are deficient in cells expressing NK cell markers in comparison to Prkdc^scid controls

♀ • spleen cells from poly(I:C) stimulated 6-8 week old mice exhibit very low levels of NK cell cytotoxic activity

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

♀ • spleens are deficient in mature T cells

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

♀ • spleens are deficient in mature T cells

decreased spleen B cell follicle number ( J:109833 )

♀ • spleens do not have detectable follicles

abnormal splenic cell ratio ( J:109833 )

♀ • two fold reduction in nucleated spleen cell numbers in comparison to Prkdc^scid controls

decreased immunoglobulin level ( J:109833 )

♀ • no detectable immunoglobulin in mice at 394-426 days of age

cellular

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

♀ • mice do not survive doses above or equal to 400cGy

neoplasm

decreased incidence of tumors by ionizing radiation induction ( J:109833 )

♀ • mice irradiated with doses below 400cGy do not exhibit thymic lymphomas in contrast to homozygous Prkdc^scid controls

homeostasis/metabolism

abnormal glucose homeostasis ( J:138005 )

♀ • streptozotocin-diabetic mice are not restored to euglycemia after receiving transplants of 1000 to 3000 IEQ, while 4000 IEQ transplant was successful in two long-term survivors

hyperglycemia ( J:138005 )

♀ • streptozotocin effectively induced hyperglycemia essentially equally in male and female mice at doses of 120to 160 mg/kg; some mice do not become hyperglycemic at all doses of streptozotocin administered

endocrine/exocrine glands

abnormal thymus morphology ( J:109833 )

♀ • thymus consists mostly of stromal cells with sporadic cyst structures

thymus cyst ( J:109833 )

♀ • sporadic cyst structures

Genotype
MGI:3620462

cx33

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(CSF2)2Ygy/0; Tg(IL3)1Ygy/0; Tg(KITLG)3Ygy/0
• Genetic Background: NOD.Cg-Prkdc^scid Tg(CSF2)2Ygy Tg(IL3)1Ygy Tg(KITLG)3Ygy

immune system

abnormal response to transplant ( J:107052 )

• blood of NOD-SCID mouse recipients remains chimeric for porcine hematopoietic cells throughout the length of the experiment (6 weeks):

decreased susceptibility to graft versus host disease ( J:107052 )

• conditioned mice were injected with splenocytes, or PBMC and BMC from sensitized porcine donors, no recipients showed detectable GVHD

Genotype
MGI:3663017

cx34

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(Ins2-Fasl)24Ach/0
• Genetic Background: NOD.Cg-Prkdc^scid Tg(Ins2-Fasl)24Ach

immune system

decreased susceptibility to autoimmune diabetes ( J:81416 )

• female mice do not develop spontaneous diabetes assessed by monitoring urine glucose levels observed for >30 weeks

increased susceptibility to autoimmune diabetes ( J:81416 )

• 6/6 mice show accelerated diabetes development determined by urine glucose level monitoring, showing the disease by ~14 days of transfer of splenocytes from diabetic NOD mice

Genotype
MGI:3622780

cx35

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(INS-Il10)#Sar/0
• Genetic Background: NOD.Cg-Prkdc^scid Tg(INS-Il10)#Sar

immune system

increased susceptibility to autoimmune diabetes ( J:66103 )

• transgenic NOD.scid mice receiving splenocytes from 12 week old nondiabetic Il10-nNOD mice develop diabetes (blood glucose level >300 mg/dl) by 4 weeks posttransfer (blood glucose >300 mg/dl), while no nontransgenic NOD.scid mice are affected over the same period;

• adoptive transfer of splenocytes from diabetic NOD mice into transgenic NOD.scid mice induces clinical disease with faster kinetics compared to nontransgenic NOD.scid mice

• transfer of splenocytes from prediabetic 8 week old NOD mice to transgenic NOD.scid mice caused diabetes after 4 weeks, while nontransgenic NOD.scid recipients didn't develop diabetes until 7 weeks posttransfer

Genotype
MGI:3618702

cx36

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(TcraAI4)1Dvs/0; Tg(TcrbAI4)1Dvs/0
• Genetic Background: NOD.Cg-Prkdc^scid Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs

hematopoietic system

abnormal CD4-positive, alpha beta T cell morphology ( J:93553 )

• mice exhibit a complete absence of CD4 T cells expressing the transgenes but transgene-expressing CD8 T cells are present

immune system

abnormal CD4-positive, alpha beta T cell morphology ( J:93553 )

• mice exhibit a complete absence of CD4 T cells expressing the transgenes but transgene-expressing CD8 T cells are present

increased susceptibility to autoimmune diabetes ( J:93553 )

• female NOD.scid transgenic mice display accerlerated diabetes development compared to standard NOD females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:93553

Genotype
MGI:3809476

cx37

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz/Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz
• Genetic Background: NOD.Cg-Tg(HLA-DRA*0101,HLA-DRB1*0101)1Dmz Prkdc^scid/Gck

mortality/aging

extended life span ( J:126700 )

• these mice live significantly longer than NOD/scid mice that do not carry the transgene

• the mean lifespan for these mice is 420.5 days compared to 247.6 days for NOD/scid controls

• controls die of thymic or splenic lymphoma

immune system

absent T cells ( J:126700 )

• T cells are absent in these mice

abnormal professional antigen presenting cell morphology ( J:126700 )

• 10-12% of peripheral blood mononuclear cells express the chimeric MHC complex

hematopoietic system

absent T cells ( J:126700 )

• T cells are absent in these mice

Genotype
MGI:3848455

cx38

• Allelic Composition: Lyst^bg/Lyst^bg; Prkdc^scid/Prkdc^scid
• Genetic Background: Not Specified

immune system

increased susceptibility to infection ( J:4752 )

• although all mice of this genotype are highly suseptible, adult female mice during the perinatal period are most at risk

• infection can involve organisms not usually regarded as mouse pathogens

Genotype
MGI:3581148

cx39

• Allelic Composition: Prkdc^scid/Prkdc^scid; Gnrh1^hpg/Gnrh1^hpg
• Genetic Background: STOCK Prkdc^scid Gnrh1^hpg/Bm

neoplasm

decreased tumor incidence ( J:14443 , J:138840 )

• ovaries grafted from (SWR x SWXJ-9)F1, which are prone to granulosa cell tumor generation, do not form granulosa cell tumors in these hypogonadal immunodeficient hosts (J:14443)

• implanted human prostate adenocarcinoma tissue assessed 3 weeks after transplantation shows two histologic patterns, undifferentiated tumors and tumors that are more differentiated but have few glandular structures, and are smaller and histologically different from the tumors from the same donor transplanted into androgen repleted immunodeficiant hosts (J:138840)

homeostasis/metabolism

decreased circulating testosterone level ( J:138840 )

• no detectable serum testosterone

abnormal circulating protein level ( J:138840 )

• serum lacks detectable prostate-specific antigen

digestive/alimentary system

small salivary gland ( J:138840 )

endocrine/exocrine glands

small salivary gland ( J:138840 )

absent seminal vesicle ( J:138840 )

♂

liver/biliary system

decreased liver weight ( J:138840 )

renal/urinary system

decreased kidney weight ( J:138840 )

reproductive system

absent seminal vesicle ( J:138840 )

♂