Phenotypes associated with this allele

• Allele Symbol: Tfrc^tm1Nca
• Allele Name: targeted mutation 1, Nancy C Andrews
• Allele ID: MGI:1859944
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tfrc^tm1Nca/Tfrc^tm1Nca	either: (involves: 129S4/SvJae * 129S6/SvEvTac) or (involves: 129S4/SvJae * C57BL/6)	MGI:2174778
ht2	Tfrc^tm1Nca/Tfrc^+	either: (involves: 129S4/SvJae * 129S6/SvEvTac) or (involves: 129S4/SvJae * C57BL/6)	MGI:2174777
cx3	Hfe^tm2Nca/Hfe^tm2Nca Tfrc^tm1Nca/Tfrc^+	involves: 129S6/SvEvTac	MGI:2655487
cx4	Hfe^tm1.1Nca/Hfe^tm1.1Nca Tfrc^tm1Nca/Tfrc^+	Not Specified	MGI:2655504

Genotype
MGI:2174778

hm1

• Allelic Composition: Tfrc^tm1Nca/Tfrc^tm1Nca
• Genetic Background: either: (involves: 129S4/SvJae * 129S6/SvEvTac) or (involves: 129S4/SvJae * C57BL/6)

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

mortality/aging

embryonic lethality, complete penetrance ( J:54107 )

• homozygous mutant embryos die before E12.5

hematopoietic system

anemia ( J:54107 )

• all mutant embryos examined after E10.5 are anemic

• however, as late as E10.5, some mutant embryos are not visibly anemic, show no signs of tissue edema or necrosis, and contain abundant circulating erythroid cells in their vasculature

decreased erythroid progenitor cell number ( J:54107 )

• in culture, yolk-sac haematopoietic progenitors from non-anaemic mutant embryos generate abnormally small erythroid colonies

abnormal embryonic erythrocyte morphology ( J:54107 )

• some embryonic erythrocytes from non-anemic mutant embryos display multiple nuclei

abnormal embryonic erythropoiesis ( J:54107 )

• mutant embryos and yolk sacs exhibit defective erythropoiesis

homeostasis/metabolism

pericardial effusion ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos exhibit obvious pericardial effusions

hydrops fetalis ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos exhibit signs of fetal hydrops

• diffuse tissue edema is observed throughout the hydropic mutant embryos

• at E9.5, non-anemic mutant embryos do not display diffuse tissue edema

hypoxia ( J:54107 )

• at E8.5-E12.5, hydropic mutant embryos display hypoxia

nervous system

kinked neural tube ( J:54107 )

• at E9.5, both anemic and non-anemic mutant embryos exhibit kinking of the neural tubes, with distortion of the neural tissue, many gaps, and dark pyknotic nuclei, suggestive of apoptotic cell death

• however, neural tube closure is not impaired

cardiovascular system

pericardial effusion ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos exhibit obvious pericardial effusions

embryo

embryonic growth retardation ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos are growth retarded

kinked neural tube ( J:54107 )

• at E9.5, both anemic and non-anemic mutant embryos exhibit kinking of the neural tubes, with distortion of the neural tissue, many gaps, and dark pyknotic nuclei, suggestive of apoptotic cell death

• however, neural tube closure is not impaired

embryo tissue necrosis ( J:54107 )

• at E8.5-E12.5, hydropic mutant embryos display diffuse necrosis in all tissues, consistent with anemia and hypoxia

• at E9.5, non-anemic mutant embryos do not display diffuse tissue necrosis

abnormal embryonic erythropoiesis ( J:54107 )

• mutant embryos and yolk sacs exhibit defective erythropoiesis

growth/size/body

embryonic growth retardation ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos are growth retarded

cellular

increased apoptosis ( J:54107 )

• at E9.5, both anemic and non-anemic mutant embryos display increased apoptotic cell death in their neural tubes and other neural tissues, as determined by TUNEL analysis

integument

pallor ( J:54107 )

• at E8.5-E12.5, many homozygous mutant embryos are severely pale

Genotype
MGI:2174777

ht2

• Allelic Composition: Tfrc^tm1Nca/Tfrc⁺
• Genetic Background: either: (involves: 129S4/SvJae * 129S6/SvEvTac) or (involves: 129S4/SvJae * C57BL/6)

hematopoietic system

hematopoietic system phenotype ( J:54107 )

N • at 11 weeks of age, heterozygotes are overtly normal and display normal hematocrits and hemoglobin levels due to a compensatory increase in erythrocyte number

N • no significant differences are observed in leukocyte or platelet cell number relative to wild-type littermates at this age

abnormal erythropoiesis ( J:54107 )

• heterozygotes exhibit defective erythropoiesis

increased erythrocyte cell number ( J:54107 )

• at 11 weeks of age, heterozygotes show a compensatory increase in red cell number relative to wild-type littermates (11.3 0.21 vs 9.5 0.41, respectively)

decreased mean corpuscular hemoglobin ( J:54107 )

• at 11 weeks of age, heterozygotes show a reduction in MCH relative to wild-type littermates (14.1 0.15 vs 17.2 0.37, respectively)

decreased mean corpuscular volume ( J:54107 )

• at 11 weeks of age, heterozygotes show a reduction in MCV relative to wild-type littermates (44.9 0.50 vs 53.4 0.80, respectively)

microcytosis ( J:54107 )

• heterozygotes display microcytic, hypochromic erythrocytes, consistent with iron deficiency

• microcytosis does not appear to result from a systemic lack of available iron, because serum transferrin saturations are relatively normal, and stainable iron is present in macrophages from heterozygous bone marrow and spleen

decreased spleen iron level ( J:54107 )

• at 11 weeks of age, heterozygotes contain significantly less g iron per gram wet weight of spleen (769.2 103.7) relative to wild-type littermates (1,185.8 137.2)

homeostasis/metabolism

abnormal iron homeostasis ( J:54107 )

• heterozygotes display decreased iron uptake by erythroid cells, leading to microcytosis and hypochromia

• however, iron saturation of serum transferrin remains unaffected

abnormal iron level ( J:54107 )

• heterozygotes show a significant reduction in tissue iron, reflecting a decrease in total body iron accumulation

decreased spleen iron level ( J:54107 )

• at 11 weeks of age, heterozygotes contain significantly less g iron per gram wet weight of spleen (769.2 103.7) relative to wild-type littermates (1,185.8 137.2)

decreased liver iron level ( J:54107 )

• at 11 weeks of age, heterozygotes contain significantly less g iron per gram wet weight of liver (108.8 10.1) relative to wild-type littermates (170.6 24.0)

immune system

decreased spleen iron level ( J:54107 )

• at 11 weeks of age, heterozygotes contain significantly less g iron per gram wet weight of spleen (769.2 103.7) relative to wild-type littermates (1,185.8 137.2)

liver/biliary system

decreased liver iron level ( J:54107 )

• at 11 weeks of age, heterozygotes contain significantly less g iron per gram wet weight of liver (108.8 10.1) relative to wild-type littermates (170.6 24.0)

digestive/alimentary system

abnormal intestinal mineral absorption ( J:54107 )

• heterozygotes display decreased intestinal iron absorption leading to a significant reduction in tissue iron levels

Genotype
MGI:2655487

cx3

• Allelic Composition: Hfe^tm2Nca/Hfe^tm2Nca; Tfrc^tm1Nca/Tfrc⁺
• Genetic Background: involves: 129S6/SvEvTac

homeostasis/metabolism

increased liver iron level ( J:62112 )

• increased hepatic iron loading

• greater hepatic iron loading than than the single Hfe^tm2Nca homozygous mutant

liver/biliary system

increased liver iron level ( J:62112 )

• increased hepatic iron loading

• greater hepatic iron loading than than the single Hfe^tm2Nca homozygous mutant

Genotype
MGI:2655504

cx4

• Allelic Composition: Hfe^tm1.1Nca/Hfe^tm1.1Nca; Tfrc^tm1Nca/Tfrc⁺
• Genetic Background: Not Specified

homeostasis/metabolism

increased liver iron level ( J:62112 )

• greater hepatic iron loading than than the single Hfe^tm1.1Nca homozygous mutant

liver/biliary system

increased liver iron level ( J:62112 )

• greater hepatic iron loading than than the single Hfe^tm1.1Nca homozygous mutant