Phenotypes associated with this allele

• Allele Symbol: Nmnat3^Gt(3020)Tgen
• Allele Name: gene trap 3020, TransGenic
• Allele ID: MGI:5638788
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nmnat3^Gt(3020)Tgen/Nmnat3^Gt(3020)Tgen	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:5823032

Genotype
MGI:5823032

hm1

• Allelic Composition: Nmnat3^Gt(3020)Tgen/Nmnat3^Gt(3020)Tgen
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

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

hematopoietic system

enlarged spleen ( J:214107 )

• mice exhibit splenomegaly from a young age

increased spleen weight ( J:214107 )

• mice show an increased spleen/body weight ratio

hemolytic anemia ( J:214107 )

• mice exhibit hemolytic anemia as early as 4 weeks of age

• anemia is primarily due to shortened lifespan of mature erythrocytes

decreased erythroid progenitor cell number ( J:214107 )

• at 8 weeks of age, most mature CD71^low/Ter119^high (P6) fraction is decreased in splenocytes, bone marrow cells, and peripheral blood

increased erythroid progenitor cell number ( J:214107 )

• a larger immature P4 fraction is also observed in bone marrow cells

• at 8 weeks of age, immature CD71^high/Ter119^high (P4) and CD71^middle/Ter119^high (P5) fractions are markedly increased in splenocytes and peripheral blood

abnormal erythrocyte morphology ( J:214107 )

• mature erythrocytes show markedly decreased ATP levels, leading to dehydration and abnormal spiked shape

• most RBCs appear as acanthocytes or echinocytes with abnormal spiked membrane projections

abnormal erythropoiesis ( J:214107 )

• at 8 weeks of age, erythropoiesis is significantly increased to compensate for the decrease in mature erythrocytes

• however, peripheral erythroid maturation is largely normal

decreased erythrocyte cell number ( J:214107 )

• however, WBC and platelet numbers are normal

• RBC numbers are decreased at 12 weeks of age

decreased hematocrit ( J:214107 )

• lower hematocrit at 12 weeks of age

decreased hemoglobin content ( J:214107 )

• lower hemoglobin concentration at 12 weeks of age

acanthocytosis ( J:214107 )

echinocytosis ( J:214107 )

reticulocytosis ( J:214107 )

• reticulocyte numbers are markedly increased at 12 weeks of age

increased spleen iron level ( J:214107 )

• spleens exhibit increased iron deposits (hemosiderin)

increased spleen red pulp amount ( J:214107 )

abnormal erythrocyte physiology ( J:214107 )

• mature erythrocytes show blockage of the glycolytic pathway at a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step due to depletion of the nicotinamide adenine dinucleotide (NAD) pool

• glycolytic flow is shifted to the pentose phosphate pathway and the blockade at GAPDH results in a reverse flow into fructose 1,6-bisphosphate from glyceraldehyde 3-phosphate (GAP), leading to ATP production failure and ultimately hemolytic anemia

increased erythrocyte clearance ( J:214107 )

• average lifespan of mature erythrocytes is only ~10 days relative to 50-60 days in wild-type controls

immune system

enlarged spleen ( J:214107 )

• mice exhibit splenomegaly from a young age

increased spleen weight ( J:214107 )

• mice show an increased spleen/body weight ratio

increased spleen iron level ( J:214107 )

• spleens exhibit increased iron deposits (hemosiderin)

increased spleen red pulp amount ( J:214107 )

homeostasis/metabolism

increased spleen iron level ( J:214107 )

• spleens exhibit increased iron deposits (hemosiderin)

abnormal enzyme/coenzyme level ( J:214107 )

• mature erythrocytes show a drastic reduction of the nicotinamide adenine dinucleotide (NAD) pool

• however, NAD levels are normal in erythroid precursor cells and other tissues (liver, heart, and skeletal muscle)

growth/size/body

enlarged spleen ( J:214107 )

• mice exhibit splenomegaly from a young age

increased spleen weight ( J:214107 )

• mice show an increased spleen/body weight ratio