Phenotypes associated with this allele

• Allele Symbol: Inpp5d^tm1Dmt
• Allele Name: targeted mutation 1, Dan Dumont
• Allele ID: MGI:1861956
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Inpp5d^tm1Dmt/Inpp5d^tm1Dmt	B6.129P2/OlaHsd-Inpp5d^tm1Dmt	MGI:5050832
hm2	Inpp5d^tm1Dmt/Inpp5d^tm1Dmt	involves: 129P2/OlaHsd	MGI:3835331
hm3	Inpp5d^tm1Dmt/Inpp5d^tm1Dmt	involves: 129P2/OlaHsd * C57BL/6	MGI:3835336

Genotype
MGI:5050832

hm1

• Allelic Composition: Inpp5d^tm1Dmt/Inpp5d^tm1Dmt
• Genetic Background: B6.129P2/OlaHsd-Inpp5d^tm1Dmt

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

mortality/aging

premature death ( J:173266 )

• 50% survival at 6 months of age

respiratory system

abnormal pulmonary alveolus morphology ( J:173266 )

• alveoli of 6 month mice are filled with lipid laden macrophage containing eosinophilic Ym1 crystals

respiratory failure ( J:173266 )

• in 50% of mice at 6 months of age

hematopoietic system

anemia ( J:173266 )

• in 4 week old mice

thrombocytopenia ( J:173266 )

• in 4 week old mice

decreased lymphocyte cell number ( J:173266 )

• reduced mature B cells in bone marrow at 10 weeks of age

decreased pre-B cell number ( J:173266 )

• reduced pre-B cells in bone marrow at 10 weeks of age

immune system

decreased lymphocyte cell number ( J:173266 )

• reduced mature B cells in bone marrow at 10 weeks of age

decreased pre-B cell number ( J:173266 )

• reduced pre-B cells in bone marrow at 10 weeks of age

increased circulating interleukin-6 level ( J:173266 )

• circulating levels elevated

• levels in bone marrow macrophage are normal but elevated in peritoneal and splenic macrophage

homeostasis/metabolism

increased circulating interleukin-6 level ( J:173266 )

• circulating levels elevated

• levels in bone marrow macrophage are normal but elevated in peritoneal and splenic macrophage

Genotype
MGI:3835331

hm2

• Allelic Composition: Inpp5d^tm1Dmt/Inpp5d^tm1Dmt
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:77739 )

• short life span

immune system

enlarged spleen ( J:77739 )

• 4-fold at 6 to 8 weeks, 8-fold at 10 weeks, and greater than 10-fold at 16 weeks

decreased B cell number ( J:77739 )

• B220+CD19+sIgM+ B cells are decreased in the bone marrow, and sIgD+sIgM+ B cells are decreased in the secondary lymphatic organs compared to in wild-type mice

increased leukocyte cell number ( J:77739 )

• the granulocyte-macrophage/monocyte populations are increased in the spleen compared to in wild-type mice

• mice exhibit an infiltration of monocyte/macrophage and granulocyte cells in the thymus, lymph nodes, liver, kidney, heart, skeletal muscle, connective tissue, exocrine pancreas, and lungs unlike in wild-type mice

abnormal leukocyte physiology ( J:77739 )

• myeloid cells exhibit decreased susceptibility to apoptosis induced by sorbitol, cycloheximide, anisomycin and Fas stimulation compared to wild-type cells

enlarged lymph nodes ( J:77739 )

hematopoietic system

enlarged spleen ( J:77739 )

• 4-fold at 6 to 8 weeks, 8-fold at 10 weeks, and greater than 10-fold at 16 weeks

decreased B cell number ( J:77739 )

• B220+CD19+sIgM+ B cells are decreased in the bone marrow, and sIgD+sIgM+ B cells are decreased in the secondary lymphatic organs compared to in wild-type mice

increased leukocyte cell number ( J:77739 )

• the granulocyte-macrophage/monocyte populations are increased in the spleen compared to in wild-type mice

• mice exhibit an infiltration of monocyte/macrophage and granulocyte cells in the thymus, lymph nodes, liver, kidney, heart, skeletal muscle, connective tissue, exocrine pancreas, and lungs unlike in wild-type mice

abnormal leukocyte physiology ( J:77739 )

• myeloid cells exhibit decreased susceptibility to apoptosis induced by sorbitol, cycloheximide, anisomycin and Fas stimulation compared to wild-type cells

growth/size/body

enlarged spleen ( J:77739 )

• 4-fold at 6 to 8 weeks, 8-fold at 10 weeks, and greater than 10-fold at 16 weeks

Genotype
MGI:3835336

hm3

• Allelic Composition: Inpp5d^tm1Dmt/Inpp5d^tm1Dmt
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism

abnormal blood coagulation ( J:121283 )

• induced thrombi are smaller, contain fewer platelets, and exhibit decreased close cell-cell contact compared to in wild-type mice

• when exposed to thrombin and atroxin, platelets fail to exhibit induced fibrin clot retraction as do wild-type cells

• however, mice are not protected against thromboembolism

abnormal platelet activation ( J:121283 )

• under thrombin stimulation, platelets fail to undergo normal degranulation and form fewer membrane extensions than wild-type cells

decreased platelet aggregation ( J:121283 )

• in vitro or under flow, platelet aggregation in response to thrombin, collagen, or thomboxane A2 is decreased compared to controls; platelet aggregates that do form are smaller

increased bleeding time ( J:121283 )

hematopoietic system

abnormal platelet activation ( J:121283 )

• under thrombin stimulation, platelets fail to undergo normal degranulation and form fewer membrane extensions than wild-type cells

decreased platelet aggregation ( J:121283 )

• in vitro or under flow, platelet aggregation in response to thrombin, collagen, or thomboxane A2 is decreased compared to controls; platelet aggregates that do form are smaller