Phenotypes associated with this allele

• Allele Symbol: Ank1^nb
• Allele Name: normoblastic anemia
• Allele ID: MGI:1856298
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ank1^nb/Ank1^nb	either: (involves: non-inbred stock) or (involves: C57BL/6) or (involves: WB/Re)	MGI:2449181
hm2	Ank1^nb/Ank1^nb	involves: C57BL/6J * WB/Re	MGI:3766445
hm3	Ank1^nb/Ank1^nb	(WB.Cg-Ank1^nb/BrkJ x B6.Cg-Ank1^nb/BrkJ)F1	MGI:4819820
ht4	Ank1^nb/Ank1^+	involves: C57BL/6J * WB/Re	MGI:3767057

Genotype
MGI:2449181

hm1

• Allelic Composition: Ank1^nb/Ank1^nb
• Genetic Background: either: (involves: non-inbred stock) or (involves: C57BL/6) or (involves: WB/Re)

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

pigmentation

abnormal skin pigmentation ( J:30699 )

• bright orange skin color at birth, fading with age

behavior/neurological

tremors ( J:11441 )

• after 6 months of age

impaired balance ( J:11441 )

• awkward, unbalanced gait develops after 6 months of age

cardiovascular system

cardiac hypertrophy ( J:30699 )

growth/size/body

cardiac hypertrophy ( J:30699 )

decreased body size ( J:30699 )

enlarged liver ( J:30699 )

enlarged spleen ( J:30699 )

• becoming 8-10% of body weight

hematopoietic system

abnormal thymus development ( J:30699 )

• the thymus is still present at 6 months of age

enlarged spleen ( J:30699 )

• becoming 8-10% of body weight

hypochromic anemia ( J:30699 )

• normocytic hypochromic anemia

decreased erythrocyte cell number ( J:30699 )

decreased hematocrit ( J:30699 )

decreased hemoglobin content ( J:30699 )

increased leukocyte cell number ( J:30699 )

immune system

abnormal thymus development ( J:30699 )

• the thymus is still present at 6 months of age

enlarged spleen ( J:30699 )

• becoming 8-10% of body weight

increased leukocyte cell number ( J:30699 )

enlarged lymph nodes ( J:30699 )

liver/biliary system

enlarged liver ( J:30699 )

gallstones ( J:6371 )

• appear in 57% of homozygotes after 6 months of age

• twice as frequent in females as in males

jaundice ( J:30699 )

• jaundice at birth but no longer obvious as adults although obvious discoloration of urine, serum, and intestines persists

reproductive system

infertility ( J:30699 )

skeleton

abnormal bone marrow morphology ( J:30699 )

• bone marrow hyperplasia

nervous system

Purkinje cell degeneration ( J:11441 )

• 50% cell loss after 6 months of age

homeostasis/metabolism

abnormal iron homeostasis ( J:30699 )

• although iron is quickly removed from the serum into erythrocytes, it does so to a lesser extent than normal and only 1/3 of the amount of iron normally seen in the femur is found there in 3 hours post iron incorporation

integument

abnormal skin pigmentation ( J:30699 )

• bright orange skin color at birth, fading with age

endocrine/exocrine glands

abnormal thymus development ( J:30699 )

• the thymus is still present at 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 1		DOID:0110916	OMIM:182900	J:11441

Genotype
MGI:3766445

hm2

• Allelic Composition: Ank1^nb/Ank1^nb
• Genetic Background: involves: C57BL/6J * WB/Re

hematopoietic system

microcytic anemia ( J:3122 )

• severe microcytic anemia is found in adults, but homozygotes are not anemic until soon after birth

abnormal erythrocyte morphology ( J:7501 , J:42526 , J:111131 )

• mutants accumulate only 50% of the normal amount of spectrin in their erythrocyte membrane skeleton, however normal levels of alpha spectrin synthesis and mRNA activity are seen (J:7501)

• red cell ghosts and membrane skeletons are smaller and more spherical than normal, although intact Triton shells can be obtained and resemble red cell ghosts in size and shape (J:42526)

• the spectrin content of red blood cell membranes is approximately half of normal, the amount of SLC4A1 that is associated with the membrane skeleton is much less than normal, more of it is in the dimeric rather than tetrameric form, and it has a greater fractional mobility (J:42526)

• electron micrographs of spread membrane skeletons from red blood cells show fewer than normal ankyrin-containing globular structures but normal skeletons and Triton shells have normal mechanical stability (J:42526)

• rotary shadowing shows increased heterogeneity of intramembrane particles in red blood cell membranes (J:42526)

• scanning electron microscopy shows exovesiculation, stomatocytes, and cells resembling acanthocytes also with an overall reduction in size of erythrocytes (J:111131)

• Percoll-stractan gradients show that the red cells are varied in both size and density (J:111131)

low mean erythrocyte cell number ( J:3122 )

• within 24 hours of birth red blood cell counts are lower than normal and continue to decrease during the early neonatal period

anisocytosis ( J:111131 )

acanthocytosis ( J:111131 )

anisopoikilocytosis ( J:111131 )

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cell protoporphyrin levels are about 10 times higher than in controls

microcytosis ( J:111131 )

poikilocytosis ( J:111131 )

spherocytosis ( J:3122 )

stomatocytosis ( J:111131 )

reticulocytosis ( J:3122 , J:42526 )

• total reticulocyte count is increased at embryonic day 18, considerably increased at 1 day of age and then decreases toward normal levels but remains elevated (J:3122)

abnormal erythrocyte physiology ( J:30033 )

• erythrocyte intracellular sodium levels are three times higher than normal, erythrocyte intracellular potassium levels are lower than normal, and ouabain induced cation flux rates in erythrocytes are approximately three times higher than normal

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cell protoporphyrin levels are about 10 times higher than in controls

abnormal iron homeostasis ( J:3122 )

• embryonic and neonatal assessment shows iron deposits in the liver but not spleen or kidney, and at embryonic day 16 hemosiderin is found in small amounds in the liver, this is increased by embryonic day 18, and is increased dramatically after birth

• adult homozygotes have extensive dposition of hemosiderin in liver macrophages and kidney proximal convoluted tubules

abnormal kidney iron level ( J:3122 )

increased liver iron level ( J:3122 )

hemosiderosis ( J:3122 )

immune system

decreased susceptibility to parasitic infection ( J:111131 )

• homozygotes are resistant to the malarial parasites, Plasmodium chabaudi adami and Plasmodium berghei and do not develop parasitemia

liver/biliary system

increased liver iron level ( J:3122 )

renal/urinary system

abnormal kidney iron level ( J:3122 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malaria		DOID:12365		J:111131

Genotype
MGI:4819820

hm3

• Allelic Composition: Ank1^nb/Ank1^nb
• Genetic Background: (WB.Cg-Ank1^nb/BrkJ x B6.Cg-Ank1^nb/BrkJ)F1

mortality/aging

preweaning lethality, incomplete penetrance ( J:162532 )

• approximately 11% die before weaning

reproductive system

infertility ( J:162532 )

cardiovascular system

cardiac hypertrophy ( J:162532 )

growth/size/body

cardiac hypertrophy ( J:162532 )

decreased body size ( J:162532 )

enlarged liver ( J:162532 )

enlarged spleen ( J:162532 )

hematopoietic system

enlarged spleen ( J:162532 )

extramedullary hematopoiesis ( J:162532 )

hemolytic anemia ( J:162532 )

abnormal erythrocyte morphology ( J:62355 )

• cell surface expression of phosphatidylserine is higher than in wild-type controls, with 7.4% of erythrocytes straining positive for phosphatidylserine versus 1.6% in wild-type controls

low mean erythrocyte cell number ( J:162532 )

• slightly more than half the normal number

decreased hematocrit ( J:162532 )

• mean hematocrit is reduced to 24.7% from 50.4% in wild-type controls

decreased hemoglobin content ( J:162532 )

• mean hemoglobin is decreased to 6.03 g/dL compared with 15.64 g/dL in wild-type controls

increased nucleated erythrocyte cell number ( J:162532 )

• approximately 6 times normal levels

anisopoikilocytosis ( J:162532 )

microcytosis ( J:62355 )

• the percentage of erythroid cells that are microcytes is much larger than in wild-type controls

poikilocytosis ( J:162532 )

schistocytosis ( J:162532 )

reticulocytosis ( J:162532 )

• mean percent of reticulocytes is substantially increased from 3.16% in wild-type controls to 59.6%

abnormal erythrocyte physiology ( J:162532 )

• sodium content of erythrocytes is elevated to 48 mEq/l from 12.4 mEq/l in wild-type controls, and the membrane cholesterol and phospholipid content is reduced

increased erythrocyte clearance ( J:162532 )

• average erythrocyte lifespan is approximately half a day

hemolysis ( J:162532 )

increased erythrocyte osmotic fragility ( J:162532 )

• increased sensitivity to osmotic lysis

homeostasis/metabolism

increased circulating bilirubin level ( J:162532 )

abnormal cardiac thrombosis ( J:62355 )

• 22% of homozygous adults display cardiac thrombi

immune system

enlarged spleen ( J:162532 )

liver/biliary system

enlarged liver ( J:162532 )

jaundice ( J:162532 )

• although not jaundiced at birth, homozygotes develop severe jaundice within hours of being born

Genotype
MGI:3767057

ht4

• Allelic Composition: Ank1^nb/Ank1⁺
• Genetic Background: involves: C57BL/6J * WB/Re

hematopoietic system

abnormal erythrocyte morphology ( J:111131 )

• occasional deformed erythrocytes are found in heterozygotes

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cells show a higher concentration of protoporphyrin than in wild-type

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cells show a higher concentration of protoporphyrin than in wild-type

immune system

decreased susceptibility to parasitic infection ( J:111131 )

• lower peak parasitaemia when infected with Plasmodium chabaudi, but normal lethal infection level occurs when infected with P. berghei