Phenotypes associated with this allele

• Allele Symbol: Hck^tm1Hev
• Allele Name: targeted mutation 1, Harold E Varmus
• Allele ID: MGI:2384049
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hck^tm1Hev/Hck^tm1Hev	B6.129S7-Hck^tm1Hev	MGI:3785295
hm2	Hck^tm1Hev/Hck^tm1Hev	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3623219
cx3	Fgr^tm1Hev/Fgr^tm1Hev Hck^tm1Hev/Hck^tm1Hev Lyn^tm1Sor/Lyn^tm1Sor	B6.Cg-Hck^tm1Hev Fgr^tm1Hev Lyn^tm1Sor	MGI:3785296
cx4	Fgr^tm1Hev/Fgr^tm1Hev Hck^tm1Hev/Hck^tm1Hev	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3623220
cx5	Hck^tm1Hev/Hck^tm1Hev Src^tm1Sor/Src^tm1Sor	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3623221

Genotype
MGI:3785295

hm1

• Allelic Composition: Hck^tm1Hev/Hck^tm1Hev
• Genetic Background: B6.129S7-Hck^tm1Hev

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

immune system

abnormal neutrophil physiology ( J:113463 )

• neutrophil degranulation following adhesion is decreased compared to in wild-type mice

abnormal inflammatory response ( J:113463 )

• following exposure to LPS then challenge with TNF at the same site to initiate a local Shwartman response, 73% mice exhibit no hemorrhages or fibrin deposition compared to the thrombohemorrhagic vasculitis observed in wild-type mice wild-type mice

• however, neutrophil migration is normal

hematopoietic system

abnormal neutrophil physiology ( J:113463 )

• neutrophil degranulation following adhesion is decreased compared to in wild-type mice

Genotype
MGI:3623219

hm2

• Allelic Composition: Hck^tm1Hev/Hck^tm1Hev
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

immune system

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

hematopoietic system

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

cellular

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

Genotype
MGI:3785296

cx3

• Allelic Composition: Fgr^tm1Hev/Fgr^tm1Hev; Hck^tm1Hev/Hck^tm1Hev; Lyn^tm1Sor/Lyn^tm1Sor
• Genetic Background: B6.Cg-Hck^tm1Hev Fgr^tm1Hev Lyn^tm1Sor

immune system

abnormal neutrophil physiology ( J:113463 )

• neutrophil degranulation after adhesion is decreased compared to in wild-type mice

abnormal inflammatory response ( J:113463 )

• following exposure to LPS then challenge with TNF at the same site to initiate a local Shwartman response, mice exhibit no hemorrhages and reduced fibrin deposition compared to the thrombohemorrhagic vasculitis observed in wild-type mice

• however, neutrophil migration is normal

hematopoietic system

abnormal neutrophil physiology ( J:113463 )

• neutrophil degranulation after adhesion is decreased compared to in wild-type mice

Genotype
MGI:3623220

cx4

• Allelic Composition: Fgr^tm1Hev/Fgr^tm1Hev; Hck^tm1Hev/Hck^tm1Hev
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

immune system

abnormal macrophage morphology ( J:59037 )

• reduced numbers of filopodia and increased lamellopodia related membrane structures

• abnormal F-actin organization

abnormal macrophage physiology ( J:59037 )

• reduced tyrosine phosphorylation of adherent peritoneal exudate macrophage and in response to antibody crosslinking of alpha5 or beta1 integrin subunits

• impaired migration

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

increased susceptibility to bacterial infection ( J:16994 )

• impaired ability to resolve infection with Listeria monocytogenes

cardiovascular system

decreased angiogenesis ( J:89137 )

• angiogenic responses to Cxcl1 and Cxcl2 are disrupted

• neutrophile responses normal but they fail to release VEGF-A in response to Cxcl1 and Cxcl2

hematopoietic system

abnormal macrophage morphology ( J:59037 )

• reduced numbers of filopodia and increased lamellopodia related membrane structures

• abnormal F-actin organization

abnormal macrophage physiology ( J:59037 )

• reduced tyrosine phosphorylation of adherent peritoneal exudate macrophage and in response to antibody crosslinking of alpha5 or beta1 integrin subunits

• impaired migration

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

cellular

impaired macrophage phagocytosis ( J:16994 )

• of antibody labeled latex beads while antibody labeled sheep red blood cells undergo normal phagocytosis

Genotype
MGI:3623221

cx5

• Allelic Composition: Hck^tm1Hev/Hck^tm1Hev; Src^tm1Sor/Src^tm1Sor
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

premature death ( J:31647 )

• approximately 50% die immediately after weaning

perinatal lethality, incomplete penetrance ( J:31647 )

• double homozygotes present at dramatically reduced proportions at 10-14 days of age

• ratios normal at E18.5

• deaths probably occurring perinatally

growth/size/body

postnatal growth retardation ( J:31647 )

• little weight gain from 14 to 50 days of age

skeleton

abnormal long bone diaphysis morphology ( J:31647 )

• proximal and distal growth zones are often fused leaving the diaphysis filled with cancellous bone

abnormal bone marrow cavity morphology ( J:31647 )

• reduced bone marrow cavity

abnormal trabecular bone morphology ( J:31647 )

• extensive development of cancellous bone reduces bone marrow cavity in long bones, vertebral bodies, sternum

• accumulations of poorly remodeled osteocartilagenous trabeculae throughout the growth zones of long bones

abnormal skeleton development ( J:31647 )

• proximal and distal growth zones are often fused leaving the diaphysis filled with cancellous bone

• normal numbers of osteoclasts found

immune system

increased macrophage cell number ( J:31647 )

• accumulation of mature macrophage in bones

decreased leukocyte cell number ( J:31647 )

• mild leucopenia at 2-4 weeks of age which is more severe at E18.5

abnormal immune system organ morphology ( J:31647 )

thymus hypoplasia ( J:31647 )

• reduced cell number in thymus

abnormal spleen morphology ( J:31647 )

abnormal spleen germinal center morphology ( J:31647 )

• absent or poorly formed germinal centers

abnormal splenic cell ratio ( J:31647 )

• increased number of colony forming units in spleen

• greatly increased numbers of immature myeloid cells

• decreased numbers of lymphoid cells

lymph node hypoplasia ( J:31647 )

• reduced number of cells in lymph nodes but structure otherwise normal

hematopoietic system

thymus hypoplasia ( J:31647 )

• reduced cell number in thymus

anemia ( J:31647 )

• mild anemia at 2-4 weeks of age which is more severe at E18.5

decreased bone marrow cell number ( J:31647 )

• reduced number of colony forming units in bone marrow

increased macrophage cell number ( J:31647 )

• accumulation of mature macrophage in bones

decreased leukocyte cell number ( J:31647 )

• mild leucopenia at 2-4 weeks of age which is more severe at E18.5

abnormal spleen morphology ( J:31647 )

abnormal spleen germinal center morphology ( J:31647 )

• absent or poorly formed germinal centers

abnormal splenic cell ratio ( J:31647 )

• increased number of colony forming units in spleen

• greatly increased numbers of immature myeloid cells

• decreased numbers of lymphoid cells

endocrine/exocrine glands

thymus hypoplasia ( J:31647 )

• reduced cell number in thymus