Phenotypes associated with this allele

• Allele Symbol: Fech^m1Pas
• Allele Name: ferrochelatase deficiency, mutation 1, Institut Pasteur
• Allele ID: MGI:1858114
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fech^m1Pas/Fech^m1Pas	involves: 129/Sv * BALB/c	MGI:2175882
ht2	Fech^m1Pas/Fech^tm1.1(FECH*)Emi	involves: 129 * BALB/cJ * C57BL/6J	MGI:6324956
cx3	Fech^m1Pas/Fech^m1Pas hem6/hem6^+	involves: 129 * BALB/c * C57BL/6	MGI:3822521
cx4	Fech^m1Pas/Fech^m1Pas hem6/hem6	involves: 129 * BALB/c * C57BL/6	MGI:3822522

Genotype
MGI:2175882

hm1

• Allelic Composition: Fech^m1Pas/Fech^m1Pas
• Genetic Background: involves: 129/Sv * BALB/c

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

homeostasis/metabolism

increased circulating bilirubin level ( J:2021 )

• mice are recognizable by the intense yellow color of their sera and gross bilirubinemia

• conjugated and total bilirubin levels in the blood are about 40-fold higher than in controls

abnormal circulating enzyme level ( J:2021 )

• transaminase activity in the serum is increased

increased circulating alkaline phosphatase level ( J:2021 )

• alkaline phosphatase activity in the serum is elevated almost 10-fold

increased porphyrin level ( J:2021 )

• porphyrin levels in erythrocytes, plasma, liver, and feces are extremely elevated

increased erythrocyte protoporphyrin level ( J:2021 )

hematopoietic system

increased spleen weight ( J:2021 )

• spleen-to-body weight ratio is significantly increased compared to controls by 15 days of age

hypochromic anemia ( J:2021 )

• mice 3 to 5 months of age have a normocytic, slightly hypochromatic anemia with a reduction in the number of red blood cells and in total hemoglobulin content

abnormal erythrocyte morphology ( J:2021 )

• polychromatophilia, anisocytosis, target cells and leptocytes are noted in blood smears from these mice

abnormal erythropoiesis ( J:2021 )

• ferrochelastase activity, important in the synthesis of hemoglobulin, is less the 7% of normal in the spleen, liver, and kidney

decreased erythrocyte cell number ( J:2021 )

• red blood cell count is reduced by almost a third compared to controls

decreased hematocrit ( J:2021 )

• hematocrit is reduced by around 25% compared to controls

decreased hemoglobin content ( J:2021 )

• hemoglobulin content is decreased by almost a third compared to controls

increased red blood cell distribution width ( J:2021 )

• the red cell volume distribution width is 34.9 compared to 21.6 in controls

anisocytosis ( J:2021 )

• is noted in blood smears

increased erythrocyte protoporphyrin level ( J:2021 )

leptocytosis ( J:2021 )

• target cells and leptocytes are noted in blood smears

polychromatophilia ( J:2021 )

• is noted in blood smears

reticulocytosis ( J:2021 )

• the percentage of reticulocytes found in the blood is four-fold higher than in controls

decreased erythrocyte osmotic fragility ( J:2021 )

• osmotic fragility of erthrocytes is slightly decreased with half the cells lysing at 0.46% saline compared to 0.53% for controls

liver/biliary system

increased liver weight ( J:2021 )

• liver-to-body weight ratio is significantly higher compared to controls by 15 days of age

jaundice ( J:2021 )

• jaundice is usually apparent and is most severe in pups and young adults

growth/size/body

distended abdomen ( J:2021 )

• enlarged liver and spleens leads to a distended abdomen by several months of age

increased liver weight ( J:2021 )

• liver-to-body weight ratio is significantly higher compared to controls by 15 days of age

increased spleen weight ( J:2021 )

• spleen-to-body weight ratio is significantly increased compared to controls by 15 days of age

reproductive system

reduced fertility ( J:2021 )

• mice have reduced fertility likely due to the poor health of the mice

behavior/neurological

decreased locomotor activity ( J:2021 )

• mice exhibit hypoactivity by several months of age

adipose tissue

decreased total body fat amount ( J:2021 )

• mice have decreased fatty tissue by several months of age

immune system

increased spleen weight ( J:2021 )

• spleen-to-body weight ratio is significantly increased compared to controls by 15 days of age

integument

skin photosensitivity ( J:2021 )

• inflammatory lesions appear on ear and backs from fluorescent lighting used in standard housing conditions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
erythropoietic protoporphyria		DOID:13270	OMIM:177000 OMIM:300752	J:2021

Genotype
MGI:6324956

ht2

• Allelic Composition: Fech^m1Pas/Fech^{tm1.1(FECH*)Emi}
• Genetic Background: involves: 129 * BALB/cJ * C57BL/6J

mortality/aging

prenatal lethality, incomplete penetrance ( J:239515 )

• fewer than the expected numbers of mice are obtained indicating prenatal mortality

growth/size/body

decreased body size ( J:239515 )

• reduced body size and mass which is already seen shortly after birth becomes more pronounced with age

postnatal growth retardation ( J:239515 )

enlarged liver ( J:239515 )

• increase in liver mass is more pronounced than in homozygous Fech^tm1Pas mice

enlarged spleen ( J:239515 )

• increase in spleen mass is more pronounced than in homozygous Fech^tm1Pas mice

hematopoietic system

enlarged spleen ( J:239515 )

• increase in spleen mass is more pronounced than in homozygous Fech^tm1Pas mice

hypochromic microcytic anemia ( J:239515 )

decreased eosinophil cell number ( J:239515 )

decreased erythrocyte cell number ( J:239515 )

• red blood cell counts are reduced

decreased hematocrit ( J:239515 )

decreased mean corpuscular hemoglobin ( J:239515 )

decreased mean corpuscular hemoglobin concentration ( J:239515 )

decreased mean corpuscular volume ( J:239515 )

thrombocytosis ( J:239515 )

reticulocytosis ( J:239515 )

homeostasis/metabolism

increased circulating bilirubin level ( J:239515 )

• most mice show elevated serum bilirubin levels that tend to increase with age

• however, serum iron concentrations are normal

increased porphyrin level ( J:239515 )

• very high levels of serum protoporphyrin IX

• however, serum levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase are not different

immune system

enlarged spleen ( J:239515 )

• increase in spleen mass is more pronounced than in homozygous Fech^tm1Pas mice

decreased eosinophil cell number ( J:239515 )

integument

skin photosensitivity ( J:239515 )

• mice exhibit skin photosensitivity, with all tested light doses eliciting acute symptoms on the exposed skin of erythema, orange exudate, and mice showing behavioral changes indicative of pain (hunched posture, reduced movement, occasional shivering, closed eyes and drawn back ears)

• pain symptoms disappear by 24 hours but the morphological changes persist for several days

liver/biliary system

abnormal liver morphology ( J:239515 )

• liver tissue appears more rigid upon palpation compared with the usual soft texture

• hepatobiliary pathology in livers, with an increase in small cells, presumably macrophages, in the liver

• many brown pigment granules are present in biliary canaliculi and portal macrophages, probably representing protoporphyrin IX deposits

enlarged liver ( J:239515 )

• increase in liver mass is more pronounced than in homozygous Fech^tm1Pas mice

abnormal bile canaliculus morphology ( J:239515 )

• many brown pigment granules are present in biliary canaliculi

jaundice ( J:239515 )

• yellowish tint of the dermis, muscles and internal organs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
erythropoietic protoporphyria		DOID:13270	OMIM:177000 OMIM:300752	J:239515

Genotype
MGI:3822521

cx3

• Allelic Composition: Fech^m1Pas/Fech^m1Pas; hem6/hem6⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6

hematopoietic system

decreased hemoglobin content ( J:142791 )

• hemoglobulin content is reduced by around 20%

increased erythrocyte protoporphyrin level ( J:142791 )

• mice have dramatically elevated levels of protoporphyrin IX (PPIX) in erythrocytes with 41.5% of erythrocytes being fluorescent, which is indicative of high levels of PPIX

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:142791 )

• mice have dramatically elevated levels of protoporphyrin IX (PPIX) in erythrocytes with 41.5% of erythrocytes being fluorescent, which is indicative of high levels of PPIX

liver/biliary system

increased liver weight ( J:142791 )

• liver weight-to-body weight ratio is three times that of controls due to hepatic porphyrin accumulation

growth/size/body

increased liver weight ( J:142791 )

• liver weight-to-body weight ratio is three times that of controls due to hepatic porphyrin accumulation

Genotype
MGI:3822522

cx4

• Allelic Composition: Fech^m1Pas/Fech^m1Pas; hem6/hem6
• Genetic Background: involves: 129 * BALB/c * C57BL/6

hematopoietic system

decreased hemoglobin content ( J:142791 )

• hemoglobulin content is reduced almost by a third compared to controls

increased erythrocyte protoporphyrin level ( J:142791 )

• mice have slightly elevated levels of protoporphyrin IX (PPIX) in erythrocytes with 4.16% of erythrocytes being fluorescent, which is indicative of high levels of PPIX

• in comparison, 41.6% of erythrocytes from Fech^m1Pas homozygotes fluoresce while only 0.08% of wild-type erythrocytes fluoresce

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:142791 )

• mice have slightly elevated levels of protoporphyrin IX (PPIX) in erythrocytes with 4.16% of erythrocytes being fluorescent, which is indicative of high levels of PPIX

• in comparison, 41.6% of erythrocytes from Fech^m1Pas homozygotes fluoresce while only 0.08% of wild-type erythrocytes fluoresce