Mouse Genome Informatics
hm1
     Ank1nb/Ank1nb
(WB.Cg-Ank1nb/BrkJ x B6.Cg-Ank1nb/BrkJ)F1
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
partial preweaning lethality ( J:162532 )
• approximately 11% die before weaning

reproductive system

cardiovascular system

growth/size

hematopoietic system
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
microcytosis ( J:62355 )
• the percentage of erythroid cells that are microcytes is much larger than in wild-type controls
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
abnormal erythrocyte osmotic lysis ( J:162532 )
• increased sensitivity to osmotic lysis

homeostasis/metabolism
thrombosis ( J:62355 )
• 22% of homozygous adults display cardiac thrombi

immune system

liver/biliary system
jaundice ( J:162532 )
• although not jaundiced at birth, homozygotes develop severe jaundice within hours of being born


Mouse Genome Informatics
hm2
     Ank1nb/Ank1nb
either: (involves: non-inbred stock) or (involves: C57BL/6) or (involves: WB/Re)
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
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

growth/size

hematopoietic system
hypochromic anemia ( J:30699 )
• normocytic hypochromic anemia
enlarged spleen ( J:30699 )
• becoming 8-10% of body weight
abnormal thymus development ( J:30699 )
• the thymus is still present at 6 months of age

immune system
enlarged spleen ( J:30699 )
• becoming 8-10% of body weight
abnormal thymus development ( J:30699 )
• the thymus is still present at 6 months of age

liver/biliary system
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

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

Mouse Models of Human Disease
 OMIM IDRef(s)
Spherocytosis, Type 1; SPH1 182900 J:11441


Mouse Genome Informatics
hm3
     Ank1nb/Ank1nb
involves: C57BL/6J * WB/Re
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
hematopoietic system
abnormal erythrocyte morphology ( J:3122 , J:7501 , J:42526 , J:111131 )
• although red blood cells at embryonic day 18 appear normal, within 24 hours of birth they are dramatically different with many microspherocytes present, and in adults many spherocytes and microspherocytes are found but almost no normal biconcave shaped red blood cells (J:3122)
• 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
microcytic anemia ( J:3122 )
• severe microcytic anemia is found in adults, but homozygotes are not anemic until soon after birth
increased erythrocyte protoporphyrin level ( J:5985 )
• red blood cell protoporphyrin levels are about 10 times higher than in controls
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

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

renal/urinary system

Mouse Models of Human Disease
 OMIM IDRef(s)
Malaria, Susceptibility to 611162 J:111131


Mouse Genome Informatics
ht4
     Ank1nb/Ank1+
involves: C57BL/6J * WB/Re
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
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