Phenotypes associated with this allele

• Allele Symbol: Hjv^tm1Nca
• Allele Name: targeted mutation 1, Nancy C Andrews
• Allele ID: MGI:3587746
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hjv^tm1Nca/Hjv^tm1Nca	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4457136
hm2	Hjv^tm1Nca/Hjv^tm1Nca	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:3588420
hm3	Hjv^tm1Nca/Hjv^tm1Nca	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5792904
ht4	Hjv^tm1Nca/Hjv^+	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:3588436
cx5	Hjv^tm1Nca/Hjv^tm1Nca Tmprss6^tm1Dgen/Tmprss6^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4457135
cx6	Hjv^tm1Nca/Hjv^+ Tmprss6^tm1Dgen/Tmprss6^tm1Dgen	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4457134
cx7	Hjv^tm1Nca/Hjv^tm1Nca Tmprss6^tm1Dgen/Tmprss6^tm1Dgen	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4457137

Genotype
MGI:4457136

hm1

• Allelic Composition: Hjv^tm1Nca/Hjv^tm1Nca
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

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

homeostasis/metabolism

abnormal iron level ( J:160248 )

• at 8 weeks, mice exhibit increased liver, heart, pancreas, and muscle iron levels compared with wild-type mice

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

hematopoietic system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

liver/biliary system

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

abnormal hepatocyte morphology ( J:160248 )

• hepatocytes exhibit increased iron accumulation compared with wild-type cells

immune system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

Genotype
MGI:3588420

hm2

• Allelic Composition: Hjv^tm1Nca/Hjv^tm1Nca
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

Histological examination of iron loading in Hjv^tm1Nca/Hjv^tm1Nca mice

mortality/aging

mortality/aging ( J:100178 )

N • no pre-natal lethality detected

homeostasis/metabolism

abnormal iron homeostasis ( J:100178 )

• greatly increased expression of ferroportin at the basolateral membrane of intestinal villi detected by immunohistochemistry

• decreased expression of hepatic hepcidin detected by northern blot analysis

abnormal iron level ( J:100178 )

• at 6 to 7 weeks of age non-heme iron is increased in the pancreas and testis

• histology shows increased iron in the exocrine and endocrine pancreas, a subset of anterior pituitary, and arteriolar endothelial cells of the testis, but no iron accumulation in splenic macrophages

decreased spleen iron level ( J:100178 )

• decrease in splenic non-heme iron

increased circulating iron level ( J:100178 )

• at 6 to 7 weeks of age serum transferrin saturation is close to 100%

increased kidney iron level ( J:100178 )

• at 6 to 7 weeks of age non-heme iron is increased in the kidney

• histology shows increased iron in distal tubules of the kidney

increased liver iron level ( J:100178 )

• at 6 to 7 weeks of age there is a 20 fold increase in non-heme iron in the liver

• histology shows pericanicular accumulation of iron in liver parenchymal cells

hemochromatosis ( J:100178 )

• phenotypically similar to juvenile hemochromatosis in human, but without the hepatic fibrosis, cardiomyopathy, diabetes, or infertility.

hematopoietic system

hematopoietic system phenotype ( J:100178 )

N • normal hemoglobin levels

decreased spleen iron level ( J:100178 )

• decrease in splenic non-heme iron

reproductive system

reproductive system phenotype ( J:100178 )

N • normal fertility in both females and males

immune system

decreased spleen iron level ( J:100178 )

• decrease in splenic non-heme iron

liver/biliary system

increased liver iron level ( J:100178 )

• at 6 to 7 weeks of age there is a 20 fold increase in non-heme iron in the liver

• histology shows pericanicular accumulation of iron in liver parenchymal cells

renal/urinary system

increased kidney iron level ( J:100178 )

• at 6 to 7 weeks of age non-heme iron is increased in the kidney

• histology shows increased iron in distal tubules of the kidney

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hemochromatosis type 2A		DOID:0111027	OMIM:602390	J:100178

Genotype
MGI:5792904

hm3

• Allelic Composition: Hjv^tm1Nca/Hjv^tm1Nca
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

homeostasis/metabolism

abnormal iron homeostasis ( J:231428 )

♂ • degree of hepatic iron overload, deregulation of hepcidin expression, and increase of hepatic BMP6 mRNA levels are quantitatively similar to those observed in mice that are homozygous for Hfe2^tm1Kpan and hemizygous for Tg(Alb-cre)21Mgn

increased liver iron level ( J:231428 )

♂ • significant increase of nonheme iron levels in liver, similar to that observed in mice that are homozygous for Hfe2^tm1Kpan and hemizygous for Tg(Alb-cre)21Mgn

liver/biliary system

increased liver iron level ( J:231428 )

♂ • significant increase of nonheme iron levels in liver, similar to that observed in mice that are homozygous for Hfe2^tm1Kpan and hemizygous for Tg(Alb-cre)21Mgn

Genotype
MGI:3588436

ht4

• Allelic Composition: Hjv^tm1Nca/Hjv⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:100178 )

N • normal hepcidin expression

Genotype
MGI:4457135

cx5

• Allelic Composition: Hjv^tm1Nca/Hjv^tm1Nca; Tmprss6^tm1Dgen/Tmprss6⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

homeostasis/metabolism

abnormal iron level ( J:160248 )

• at 8 weeks, mice exhibit increased liver, heart, pancreas, and muscle iron levels compared with wild-type mice

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

hematopoietic system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

liver/biliary system

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

abnormal hepatocyte morphology ( J:160248 )

• hepatocytes exhibit increased iron accumulation compared with wild-type cells

immune system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

Genotype
MGI:4457134

cx6

• Allelic Composition: Hjv^tm1Nca/Hjv⁺; Tmprss6^tm1Dgen/Tmprss6^tm1Dgen
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

endocrine/exocrine glands

decreased pancreas iron level ( J:160248 )

• at 8 weeks

hematopoietic system

microcytic anemia ( J:160248 )

• at 8 weeks

decreased erythrocyte cell number ( J:160248 )

decreased hematocrit ( J:160248 )

decreased hemoglobin content ( J:160248 )

decreased mean corpuscular hemoglobin concentration ( J:160248 )

decreased mean corpuscular volume ( J:160248 )

increased red blood cell distribution width ( J:160248 )

homeostasis/metabolism

abnormal iron level ( J:160248 )

• at 8 weeks, mice exhibit decreased liver, heart, pancreas, and skeletal muscle iron levels compared with wild-type mice

• however, spleen iron levels are normal

decreased heart iron level ( J:160248 )

• decreased at 8 weeks

decreased pancreas iron level ( J:160248 )

• at 8 weeks

decreased liver iron level ( J:160248 )

• at 8 weeks

liver/biliary system

decreased liver iron level ( J:160248 )

• at 8 weeks

cardiovascular system

decreased heart iron level ( J:160248 )

• decreased at 8 weeks

integument

sparse hair ( J:160248 )

Genotype
MGI:4457137

cx7

• Allelic Composition: Hjv^tm1Nca/Hjv^tm1Nca; Tmprss6^tm1Dgen/Tmprss6^tm1Dgen
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

homeostasis/metabolism

abnormal iron level ( J:160248 )

• at 8 weeks, mice exhibit increased liver, heart, pancreas, and muscle iron levels compared with wild-type mice

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

hematopoietic system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

liver/biliary system

increased liver iron level ( J:160248 )

• at 8 weeks, specifically in hepatocytes

abnormal hepatocyte morphology ( J:160248 )

• hepatocytes exhibit increased iron accumulation compared with wild-type cells

immune system

abnormal macrophage morphology ( J:160248 )

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

decreased spleen iron level ( J:160248 )

• spleen iron levels are decreased compared to in wild-type mice

• splenic macrophages exhibit decreased iron levels compared with wild-type cells

integument

integument phenotype ( J:160248 )

N • mice retain full body hair