Phenotypes associated with this allele

• Allele Symbol: Ptpn2^tm1Mtr
• Allele Name: targeted mutation 1, Michel L Tremblay
• Allele ID: MGI:3044910
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptpn2^tm1Mtr/Ptpn2^tm1Mtr	B6.129S4(C)-Ptpn2^tm1Mtr	MGI:5436253
hm2	Ptpn2^tm1Mtr/Ptpn2^tm1Mtr	C.129S4-Ptpn2^tm1Mtr	MGI:5436252
hm3	Ptpn2^tm1Mtr/Ptpn2^tm1Mtr	involves: 129S4/SvJae * BALB/c	MGI:3044932

Genotype
MGI:5436253

hm1

• Allelic Composition: Ptpn2^tm1Mtr/Ptpn2^tm1Mtr
• Genetic Background: B6.129S4(C)-Ptpn2^tm1Mtr

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

Runtiness of Ptpn2^tm1Mtr/Ptpn2^tm1Mtr and Ptpn2^tm2.1Ttig/Ptpn2^tm2.1Ttig mice

mortality/aging

premature death ( J:186843 )

• median survival is 32 days

• Background Sensitivity: median survival is reduced for mice on a BALB/c background compared to mice on a C57BL/6 background

skeleton

skeleton phenotype ( J:186843 )

N • Background Sensitivity: unlike mice on A BALB/c background, no overt difference in bone size or trabecular bone volume is detected at P14

decreased bone mineral content ( J:186843 )

increased bone mineral density ( J:186843 )

• increased when normalized to body weight

• Background Sensitivity: increase in BMD is greater in mice on a BALB/c background compared to those on a C57BL/6 background

growth/size/body

decreased lean body mass ( J:186843 )

• decrease in total lean mass but not in lean mass normalized to total body weight

decreased body size ( J:186843 )

adipose tissue

decreased total body fat amount ( J:186843 )

hematopoietic system

hematopoietic system phenotype ( J:186843 )

N • Background Sensitivity: unlike mice on a BALB/c background, splenomegaly is not detected in mice on a C57BL/6 background

thymus atrophy ( J:186843 )

• at P29

abnormal bone marrow cell number ( J:186843 )

• Background Sensitivity: decrease in the number of CD11b+ cells in the bone marrow in mice on a C57BL/6 background but not in mice on a BALB/c background

• more than an 80% decrease in CD117-Ter119+ cells in the bone marrow

decreased bone marrow cell number ( J:186843 )

decreased erythroid progenitor cell number ( J:186843 )

• more than an 80% decrease in CD117+Ter119- progenitor cells

decreased erythrocyte cell number ( J:186843 )

• more than an 80% decrease in CD117-Ter119+ cells in the bone marrow

• Background Sensitivity: the reduction in the number of circulating erythrocytes is more severe on a BALB/c background compared to a C57BL/6 background

decreased B cell number ( J:186843 )

• dramatic reduction in total B220+ B cells

• Background Sensitivity: decrease in the spleen is more severe in mice on a C57BL/6 background at P28 compared to mice on a BALB/c background at P28, while the reverse is seen in lymph nodes

decreased immature B cell number ( J:186843 )

• dramatic decrease in IgM^-IgD^-B220^lo progenitor B cells and IgM^hiIgD^loB220^lo immature B cells at P28

decreased mature B cell number ( J:186843 )

• dramatic reduction in IgM^intIgD^hiB220^hi mature recirculating B cells at P28

decreased B-1 B cell number ( J:186843 )

• dramatic reduction at P28

decreased follicular B cell number ( J:186843 )

• dramatic reduction at P28

decreased marginal zone B cell number ( J:186843 )

• dramatic reduction at P28

decreased T cell number ( J:186843 )

decreased thymocyte number ( J:186843 )

• profound decrease at P29

decreased double-positive T cell number ( J:186843 )

• in the thymus at P18 with a profound decrease at P29

decreased CD4-positive, alpha-beta T cell number ( J:186843 )

• profound decrease at P29

decreased single-positive T cell number ( J:186843 )

• profound decrease at P29

immune system

thymus atrophy ( J:186843 )

• at P29

decreased B cell number ( J:186843 )

• dramatic reduction in total B220+ B cells

• Background Sensitivity: decrease in the spleen is more severe in mice on a C57BL/6 background at P28 compared to mice on a BALB/c background at P28, while the reverse is seen in lymph nodes

decreased immature B cell number ( J:186843 )

• dramatic decrease in IgM^-IgD^-B220^lo progenitor B cells and IgM^hiIgD^loB220^lo immature B cells at P28

decreased mature B cell number ( J:186843 )

• dramatic reduction in IgM^intIgD^hiB220^hi mature recirculating B cells at P28

decreased B-1 B cell number ( J:186843 )

• dramatic reduction at P28

decreased follicular B cell number ( J:186843 )

• dramatic reduction at P28

decreased marginal zone B cell number ( J:186843 )

• dramatic reduction at P28

decreased T cell number ( J:186843 )

decreased thymocyte number ( J:186843 )

• profound decrease at P29

decreased double-positive T cell number ( J:186843 )

• in the thymus at P18 with a profound decrease at P29

decreased CD4-positive, alpha-beta T cell number ( J:186843 )

• profound decrease at P29

decreased single-positive T cell number ( J:186843 )

• profound decrease at P29

abnormal lymph node morphology ( J:186843 )

• trend towards increased weight but about a 2.9 fold decrease in cellularity

endocrine/exocrine glands

thymus atrophy ( J:186843 )

• at P29

decreased thymocyte number ( J:186843 )

• profound decrease at P29

Genotype
MGI:5436252

hm2

• Allelic Composition: Ptpn2^tm1Mtr/Ptpn2^tm1Mtr
• Genetic Background: C.129S4-Ptpn2^tm1Mtr

Runtiness of Ptpn2^tm1Mtr/Ptpn2^tm1Mtr and Ptpn2^tm2.1Ttig/Ptpn2^tm2.1Ttig mice

mortality/aging

premature death ( J:186843 )

• Background Sensitivity: median survival is reduced for mice on a BALB/c background compared to mice on a C57BL/6 background

• median survival is 21 days

postnatal lethality, incomplete penetrance ( J:186843 )

• develop morbidity by 18-21 days of age

skeleton

abnormal skeleton morphology ( J:186843 )

• small skeleton at P14

abnormal long bone morphology ( J:186843 )

decreased diameter of femur ( J:186843 )

• decreased width at P14

short femur ( J:186843 )

• at P14

abnormal long bone epiphyseal ossification zone morphology ( J:186843 )

• delayed development of the secondary ossification centre at P14 but not at P21

abnormal bone structure ( J:186843 )

decreased bone mineral content ( J:186843 )

increased bone mineral density ( J:186843 )

• increased when normalized to body weight

• Background Sensitivity: increase in BMD is greater in mice on a BALB/c background compared to those on a C57BL/6 background

increased trabecular bone volume ( J:186843 )

• in the proximal tibial metaphysis

abnormal bone trabecula morphology ( J:186843 )

• increased trabecular thickness and reduced trabecular thickness in the proximal tibial metaphysis

increased bone trabecula number ( J:186843 )

• in the proximal tibial metaphysis at P14

abnormal ossification involved in bone maturation ( J:186843 )

• decrease in bone remodeling indicated by a reduction in osteoid deposition and a significant reduction in osteoblast surface

growth/size/body

decreased lean body mass ( J:186843 )

• decrease in total lean mass but not in lean mass normalized to total body weight

decreased body size ( J:186843 )

• at 18-21 days of age

enlarged spleen ( J:186843 )

• Background Sensitivity: at P18 in mice on a BALB/c background but not in mice on a C57BL/6 background

adipose tissue

decreased total body fat amount ( J:186843 )

hematopoietic system

thymus atrophy ( J:186843 )

• at P18 with a 4-5 fold decrease in total cellularity

enlarged spleen ( J:186843 )

• Background Sensitivity: at P18 in mice on a BALB/c background but not in mice on a C57BL/6 background

abnormal T cell differentiation ( J:186843 )

abnormal negative T cell selection ( J:186843 )

• modest increase in the number of cell undergoing negative selection at P14-16

abnormal positive T cell selection ( J:186843 )

• increase in the number of cell undergoing positive selection at P18

abnormal bone marrow cell number ( J:186843 )

• more than an 80% decrease in CD117-Ter119+ cells in the bone marrow

decreased bone marrow cell number ( J:186843 )

decreased erythroid progenitor cell number ( J:186843 )

• more than an 80% decrease in CD117+Ter119- progenitor cells

decreased erythrocyte cell number ( J:186843 )

• more than an 80% decrease in CD117-Ter119+ cells in the bone marrow

• Background Sensitivity: the reduction in the number of circulating erythrocytes is more severe on a BALB/c background compared to a C57BL/6 background

decreased B cell number ( J:186843 )

• dramatic reduction in total B220+ B cells

decreased immature B cell number ( J:186843 )

• dramatic decrease in IgM^-IgD^-B220^lo progenitor B cells and IgM^hiIgD^loB220^lo immature B cells at P18

decreased mature B cell number ( J:186843 )

• dramatic reduction in IgM^intIgD^hiB220^hi mature recirculating B cells at P18

decreased B-1 B cell number ( J:186843 )

• dramatic reduction at P18

decreased follicular B cell number ( J:186843 )

• dramatic reduction at P18

decreased marginal zone B cell number ( J:186843 )

• dramatic reduction at P18

abnormal T cell subpopulation ratio ( J:186843 )

• increase in the single positive to double positive ratio at P18

decreased T cell number ( J:186843 )

decreased thymocyte number ( J:186843 )

• 4-5 fold decrease in total cellularity at P18

decreased double-positive T cell number ( J:186843 )

• in the thymus at P18

decreased CD4-positive, alpha-beta T cell number ( J:186843 )

• particular decrease in the CD4+ lineage in the thymus at P18

decreased single-positive T cell number ( J:186843 )

• in the thymus at P18

increased splenocyte number ( J:186843 )

• Background Sensitivity: dramatic increase in total CD11b+ and CD11b+Gr+ myeloid cells in mice on a BALB/c background but not in mice on a C57BL/6 background

behavior/neurological

abnormal pilomotor reflex ( J:186843 )

• piloerection by 18-21 days of age in morbid mice

hunched posture ( J:186843 )

• by 18-21 days of age in morbid mice

decreased locomotor activity ( J:186843 )

• by 18-21 days of age in morbid mice

digestive/alimentary system

diarrhea ( J:186843 )

• by 18-21 days of age in morbid mice

limbs/digits/tail

decreased diameter of femur ( J:186843 )

• decreased width at P14

short femur ( J:186843 )

• at P14

immune system

thymus atrophy ( J:186843 )

• at P18 with a 4-5 fold decrease in total cellularity

enlarged spleen ( J:186843 )

• Background Sensitivity: at P18 in mice on a BALB/c background but not in mice on a C57BL/6 background

abnormal T cell differentiation ( J:186843 )

abnormal negative T cell selection ( J:186843 )

• modest increase in the number of cell undergoing negative selection at P14-16

abnormal positive T cell selection ( J:186843 )

• increase in the number of cell undergoing positive selection at P18

decreased double-positive T cell number ( J:186843 )

• in the thymus at P18

decreased B cell number ( J:186843 )

• dramatic reduction in total B220+ B cells

decreased immature B cell number ( J:186843 )

• dramatic decrease in IgM^-IgD^-B220^lo progenitor B cells and IgM^hiIgD^loB220^lo immature B cells at P18

decreased mature B cell number ( J:186843 )

• dramatic reduction in IgM^intIgD^hiB220^hi mature recirculating B cells at P18

decreased B-1 B cell number ( J:186843 )

• dramatic reduction at P18

decreased follicular B cell number ( J:186843 )

• dramatic reduction at P18

decreased marginal zone B cell number ( J:186843 )

• dramatic reduction at P18

abnormal T cell subpopulation ratio ( J:186843 )

• increase in the single positive to double positive ratio at P18

decreased T cell number ( J:186843 )

decreased thymocyte number ( J:186843 )

• 4-5 fold decrease in total cellularity at P18

decreased CD4-positive, alpha-beta T cell number ( J:186843 )

• particular decrease in the CD4+ lineage in the thymus at P18

decreased single-positive T cell number ( J:186843 )

• in the thymus at P18

increased splenocyte number ( J:186843 )

• Background Sensitivity: dramatic increase in total CD11b+ and CD11b+Gr+ myeloid cells in mice on a BALB/c background but not in mice on a C57BL/6 background

abnormal lymph node morphology ( J:186843 )

• Background Sensitivity: lymph node size is similar to controls but cellularity is reduced about 5 fold in mice on a BALB/c background but not in mice on a C57BL/6 background

endocrine/exocrine glands

thymus atrophy ( J:186843 )

• at P18 with a 4-5 fold decrease in total cellularity

decreased thymocyte number ( J:186843 )

• 4-5 fold decrease in total cellularity at P18

Genotype
MGI:3044932

hm3

• Allelic Composition: Ptpn2^tm1Mtr/Ptpn2^tm1Mtr
• Genetic Background: involves: 129S4/SvJae * BALB/c

Decreased number of stromal cells in Ptpn2^tm1Mtr/Ptpn2^tm1Mtr bone marrow

mortality/aging

premature death ( J:42595 )

• all are dead by 5 weeks of age

behavior/neurological

hunched posture ( J:42595 )

• develops between 3 and 5 weeks of age

decreased locomotor activity ( J:42595 )

• develops between 3 and 5 weeks of age

digestive/alimentary system

diarrhea ( J:42595 )

• develops between 3 and 5 weeks of age

growth/size/body

postnatal growth retardation ( J:42595 )

• modest growth retardation by 2 weeks of age

enlarged spleen ( J:42595 )

• splenomegaly by 3rd week

spleen hyperplasia ( J:42595 )

• by 3rd week

• total cellularity of spleen significantly elevated, peaking around 3 weeks of age

hematopoietic system

abnormal thymus involution ( J:42595 )

• thymus involuted by day 21

abnormal erythropoiesis ( J:42595 )

• impaired erythropoiesis

decreased double-positive T cell number ( J:42595 )

anemia ( J:42595 )

• severe anemia by 21st day

abnormal bone marrow cell morphology/development ( J:42595 )

• number of stromal cells is decreased in the bone marrow

decreased hematocrit ( J:42595 )

• decreasing with age

abnormal B cell number ( J:42595 )

decreased B cell number ( J:42595 )

• spleens showed moderate reductions in B cells at days 13 and 17 and marked reductions by day 21

• cellularity and percentage of B cells reduced 9 fold by 21 days of age in bone marrow

increased B cell number ( J:42595 )

• increased percentage of B cells in lymph nodes

increased mature B cell number ( J:42595 )

• lymph nodes showed increased mature B cells on days 13, 17, and 21

increased pre-B cell number ( J:42595 )

• lymph nodes showed increased pre-B cells on days 13, 17, and 21

increased macrophage cell number ( J:42595 )

• increased in spleen but not lymph nodes

abnormal spleen morphology ( J:42595 )

enlarged spleen ( J:42595 )

• splenomegaly by 3rd week

spleen hyperplasia ( J:42595 )

• by 3rd week

• total cellularity of spleen significantly elevated, peaking around 3 weeks of age

increased spleen red pulp amount ( J:42595 )

• expansion seen in some spleens

immune system

abnormal thymus involution ( J:42595 )

• thymus involuted by day 21

decreased double-positive T cell number ( J:42595 )

abnormal B cell number ( J:42595 )

decreased B cell number ( J:42595 )

• spleens showed moderate reductions in B cells at days 13 and 17 and marked reductions by day 21

• cellularity and percentage of B cells reduced 9 fold by 21 days of age in bone marrow

increased B cell number ( J:42595 )

• increased percentage of B cells in lymph nodes

increased mature B cell number ( J:42595 )

• lymph nodes showed increased mature B cells on days 13, 17, and 21

increased pre-B cell number ( J:42595 )

• lymph nodes showed increased pre-B cells on days 13, 17, and 21

increased macrophage cell number ( J:42595 )

• increased in spleen but not lymph nodes

abnormal spleen morphology ( J:42595 )

enlarged spleen ( J:42595 )

• splenomegaly by 3rd week

spleen hyperplasia ( J:42595 )

• by 3rd week

• total cellularity of spleen significantly elevated, peaking around 3 weeks of age

increased spleen red pulp amount ( J:42595 )

• expansion seen in some spleens

enlarged lymph nodes ( J:42595 )

• lymphadenopathy by 3rd week

lymph node hyperplasia ( J:42595 )

• total cellularity of lymph nodes significantly elevated, peaking around 3 weeks of age

• hyperplasia of follicles in lymph nodes

increased interferon-gamma secretion ( J:90541 )

• IFN-gamma production increased in liver by 3 days of age

increased interleukin-12 secretion ( J:90541 )

• IL-12 is massively up regulated in liver at 3 days of age and by 2 weeks in salivary gland and spleen as well

increased tumor necrosis factor secretion ( J:90541 )

• production elevated by 3 days of age in liver but not thymus

• levels increase still further by 2 weeks and also elevated in thymus

abnormal inflammatory response ( J:90541 )

increased inflammatory response ( J:90541 )

• focal inflammatory infiltration of salivary gland and stomach by 1 week of age

• myocarditis by 2nd week

• severity of inflammatory lesions increase with age

vision/eye

narrow eye opening ( J:42595 )

• progressive closure of eyelids with time

• develops between 3 and 5 weeks of age

endocrine/exocrine glands

abnormal thymus involution ( J:42595 )

• thymus involuted by day 21