Phenotypes associated with this allele

• Allele Symbol: Ahsp^tm1Mjwe
• Allele Name: targeted mutation 1, Mitchell J Weiss
• Allele ID: MGI:2449154
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ahsp^tm1Mjwe/Ahsp^tm1Mjwe	involves: 129 * C57BL/6	MGI:2449159
hm2	Ahsp^tm1Mjwe/Ahsp^tm1Mjwe	involves: 129S6/SvEvTac * C57BL/6	MGI:3769322
ht3	Ahsp^tm1Mjwe/Ahsp^+	involves: 129 * C57BL/6	MGI:2449160
ht4	Ahsp^tm1Mjwe/Ahsp^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3769336
cx5	Ahsp^tm1Mjwe/Ahsp^+ Hbb-b1^tm1Unc/Hbb-b1^+ Hbb-b2^tm1Unc/Hbb-b2^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3769340
cx6	Ahsp^tm1Mjwe/Ahsp^tm1Mjwe Hbb-b1^tm1Unc/Hbb-b1^+ Hbb-b2^tm1Unc/Hbb-b2^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3769341

Genotype
MGI:2449159

hm1

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp^tm1Mjwe
• Genetic Background: involves: 129 * C57BL/6

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

hematopoietic system

abnormal erythropoiesis ( J:77038 )

• homozygotes display erythrocyte abnormalities likely to result from a pathological accumulation of precipitated alpha-haemoglobin

abnormal hemoglobin ( J:77038 )

• homozygotes exhibit denatured hemoglobin inclusions in mutant erythrocytes, suggesting accumulation of precipitated alpha-haemoglobin

acanthocytosis ( J:77038 )

• homozygotes exhibit spiculated erythrocytes containing denatured hemoglobin inclusions (Heinz bodies) that stain with crystal violet

• however, no significant differences in hematocrit, erythrocyte number, mean corpuscular volume, mean corpuscular hemoglobin or mean corpuscular hemoglobin concentration are observed

increased number of Heinz bodies ( J:77038 )

reticulocytosis ( J:77038 )

• homozygotes show a ~3-fold increase in blood reticulocyte counts relative to wild-type mice, indicating a shortened erythrocyte half-life

Genotype
MGI:3769322

hm2

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp^tm1Mjwe
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

hematopoietic system

enlarged spleen ( J:94421 )

• spleen is significantly enlarged

abnormal definitive hematopoiesis ( J:94421 )

• there is an elevated level of apoptotic erythroid precursors in mutant spleens

anemia ( J:94421 )

• mice show mild anemia associated with small red blood cells

increased erythroid progenitor cell number ( J:94421 )

• spleen shows increased proportion of erythroid precursors

• cultured spleen cells show a higher proportion of burst-forming unit erythroid and colony-forming unit erythroid cells (BFUe and CFUe's)

abnormal erythrocyte morphology ( J:94421 )

• erythrocytes exhibit a half-life of 12 days, compared to 22 days of cells from wild-type littermates

• erythroid precursors show significant hyperplasia in the spleen and to a lesser degree in the bone marrow

decreased hematocrit ( J:94421 )

• hematocrit is reduced to 48.7% from 55.8% in wild-type

abnormal hemoglobin ( J:94421 )

• erythrocytes contain alpha- and beta-globin precipitates; membrane-associated globin chains are not observed in control littermates

abnormal hemoglobin content ( J:94421 )

increased hemoglobin concentration distribution width ( J:94421 )

• variation in hemoglobin content of mutant erythrocytes, evidenced by increased hemoglobin distribution width (HDW), is observed

decreased mean corpuscular hemoglobin ( J:94421 )

decreased mean corpuscular volume ( J:94421 )

• mice have small red blood cells with low mean corpuscular hemoglobin (13.6 pg vs 16.2 pg in wild-type)

anisocytosis ( J:94421 )

acanthocytosis ( J:94421 )

• spiculated red blood cells can be seen in blood smears

anisopoikilocytosis ( J:94421 )

• blood smears show morphologic abnormalities such as irregular size and shape

increased number of Heinz bodies ( J:94421 )

• some erythrocytes have inclusion bodies composed of denatured hemoglobin chains (Heinz bodies)

leptocytosis ( J:94421 )

• target red blood cells (codocytes) can be seen in blood smears

polychromatophilia ( J:94421 )

• large inclusions are present only in polychromatophilic cells, suggesting accelerated erythrocyte destruction

reticulocytosis ( J:94421 )

• reticulocyte count is elevated (to 4.4% from 2.2% in wild-type)

cellular

increased cellular sensitivity to oxidative stress ( J:94421 )

• mutants show a larger decrease in hematocrit after phenylhydrazine treatment resulting from hemolytic anemia compared to control littermates

oxidative stress ( J:94421 )

• mutant erythrocytes display intrinsically elevated oxidative stress

• mice have increased levels of reactive oxygen species catalyzed by alpha-hemoglobin

immune system

enlarged spleen ( J:94421 )

• spleen is significantly enlarged

growth/size/body

enlarged spleen ( J:94421 )

• spleen is significantly enlarged

Genotype
MGI:2449160

ht3

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp⁺
• Genetic Background: involves: 129 * C57BL/6

hematopoietic system

reticulocytosis ( J:77038 )

• heterozygotes show a mild elevation in blood reticulocyte counts relative to wild-type mice, suggesting a subtle erythroid phenotype

Genotype
MGI:3769336

ht4

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

hematopoietic system

increased number of Heinz bodies ( J:94421 )

• erythrocytes contain inclusion bodies composed of denatured hemoglobin chains (Heinz bodies)

Genotype
MGI:3769340

cx5

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp⁺; Hbb-b1^tm1Unc/Hbb-b1⁺; Hbb-b2^tm1Unc/Hbb-b2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

hematopoietic system

anemia ( J:94421 )

• embryos are anemic

decreased hematocrit ( J:94421 )

• decreased to 27.5% from ~55% in wild-type embryos

integument

pallor ( J:94421 )

• embryos are pale

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:94421

Genotype
MGI:3769341

cx6

• Allelic Composition: Ahsp^tm1Mjwe/Ahsp^tm1Mjwe; Hbb-b1^tm1Unc/Hbb-b1⁺; Hbb-b2^tm1Unc/Hbb-b2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:94421 )

• live-born offspring are reduced by ~50% relative to expected values (observed - 6; expected - 13.7)

hematopoietic system

anemia ( J:94421 )

• embryos are anemic

• survivors are more anemic in early adulthood than thalassemic mice that are wild-type or heterozygous for Eraf expression

abnormal erythrocyte morphology ( J:94421 )

• more erythrocytes containing inclusion bodies are observed in mutants compared to mice with thalassemia alone

decreased hematocrit ( J:94421 )

• decreased to 22.6% from 27.5% in thalassemic embryos with wild-type or heterozygous Eraf expression (or ~55% in wild-type embryos); variability is larger with Eraf-deficiency with hematocrit values in some mice of ~16%

increased hemoglobin concentration distribution width ( J:94421 )

• greater variation in hemoglobin content of mutant erythrocytes, evidenced by increased hemoglobin distribution width (HDW), is observed compared to thalassemic mice that are wild-type or heterozygous for Eraf expression

decreased mean corpuscular volume ( J:94421 )

• mice have smaller red blood cells with lower mean corpuscular volume than thalassemic mice alone

increased nucleated erythrocyte cell number ( J:94421 )

• increased numbers of nucleated liver-derived definitive erythrocytes are detected

anisocytosis ( J:94421 )

• greater variation in size of erythrocytes as shown by increased red blood cell distribution width (RBW) compared to thalassemic mice that are wild-type or heterozygous for Eraf expression

increased number of Heinz bodies ( J:94421 )

• erythrocytes have more prominent inclusion bodies (composed of denatured hemoglobin chains (Heinz bodies)) than thalassemic mice that are wild-type or heterozygous for Eraf expression

• erythrocytes show predominantly alpha-globin precipitate

integument

pallor ( J:94421 )

• embryos are pale

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:94421