Phenotypes Associated with This Genotype

Genotype
MGI:6509037

• Allelic Composition: Eps15^{tm1c(KOMP)Wtsi}/Eps15^{tm1c(KOMP)Wtsi}; Eps15l1^tm2.1Noff/Eps15l1^tm2.1Noff; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL

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

hematopoietic system

abnormal erythropoiesis ( J:272122 )

• maturation of RBCs is impaired

extramedullary hematopoiesis ( J:272122 )

• Perls' Prussian blue staining suggests increased erythropoiesis in the spleen of adult mice

• however, no tissue iron overload is observed in the spleen or liver

anemia ( J:272122 )

• adult mice are anemic as revealed by a significant reduction in all parameters analyzed (RBC, MCV, hematocrit and hemoglobin)

hypochromic microcytic anemia ( J:272122 )

• adult mice suffer from microcytic hypochromic anemia due to a cell-autonomous defect in iron internalization; o-dianisidine staining confirmed that RBCs are hypochromic

decreased erythrocyte cell number ( J:272122 )

decreased hematocrit ( J:272122 )

decreased hemoglobin content ( J:272122 )

decreased mean corpuscular volume ( J:272122 )

anisopoikilocytosis ( J:272122 )

• May-Grunwald-Giemsa staining of blood smears revealed a great variation in the size and shape of RBCs

reticulocytosis ( J:272122 )

• mice exhibit twice as many reticulocytes (thiazole orange-positive cells) in the blood, suggesting that maturation of RBCs is impaired

homeostasis/metabolism

increased circulating iron level ( J:272122 )

• adult mice show increased serum iron levels, indicating that iron absorption is not impaired

• however, serum transferrin and ferritin levels are normal

cellular

abnormal endocytosis ( J:272122 )

• surface transferrin receptor (TfR) expression is retained in ~50% of mature RBCs (thiazole orange-negative cells), whereas it is virtually absent (as expected) in wild-type controls

• a significantly higher fraction of thiazole orange-positive cells retain TfR surface expression relative to wild-type controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypochromic microcytic anemia		DOID:0050642	OMIM:206100 OMIM:615234	J:272122