Mouse Genome Informatics
hm1
    Hbath-J/Hbath-J
involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no homozygous embryos can be detected by E6.5, the percentage of homozygotes in heterozygous intercross matings is reduced to only 7.7% rather than the expected 25% by E5.5, but homozygotes implant and are found at normal numbers at implantation
• degeneration of homozygous embryos begins on E5.5 and is complete by E6.5

embryogenesis
• homozygous blastocysts have fewer trophectoderm cells, 78.6% of normal, and slightly fewer than normal cells of the inner cell mass and therefore have fewer total cells than normal
• cells of the inner cell mass of homozygous blastocysts hatched from the zona pellucida and grown in culture become necrotic and and do not remain associated with the trophoblast monolayer, as happens in wildtype blastocyst cultures


Mouse Genome Informatics
ht2
    Hbath-J/Hba+
B6.Cg-Hbath-J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
other phenotype
• offspring of heterozygous females, both wild-type and heterozygous offspring, have lower body weights than the offspring of wild-type mothers bred to heterozygous males


Mouse Genome Informatics
ht3
    Hbath-J/Hba+
involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected heterozygous mice are found at weaning (39% compared to the expected 50%)

growth/size

hematopoietic system
• low blood hemoglobin levels

Mouse Models of Human Disease
OMIM IDRef(s)
Alpha-Thalassemia 604131 J:32654 , J:45721


Mouse Genome Informatics
cx4
    Hba-a1tm1Ywk/Hbath-J
involves: 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants do not survive as newborns

growth/size
• at E19.5, mutant fetuses are smaller than control fetuses

hematopoietic system
• at E17.5, mutant erythrocytees display notable anisocytosis, poikilocytosis, polychromasia, and targeting, characteristic of severe thalassemia
• virtually all mutant erythrocytes exhibit hemoglobin H inclusions
• at E17.5, hemoglobin H (beta4) is the major component constituting 55%-65% of total hemoglobin, as shown by isoelectric focusing electrophoresis
• at E17.5, mutant fetuses display severe hemolytic anemia
• at E17.5, mutant fetuses exhibit very high reticulocyte counts

integument
• at E19.5, mutant fetuses are paler than control fetuses

Mouse Models of Human Disease
OMIM IDRef(s)
Hemoglobin--Alpha Locus 1; HBA1 141800 J:35018