Phenotypes associated with this allele

• Allele Symbol: Gsn^tm1Djk
• Allele Name: targeted mutation 1, David J Kwiatkowski
• Allele ID: MGI:2179509
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gsn^tm1Djk/Gsn^tm1Djk	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)	MGI:2684175
hm2	Gsn^tm1Djk/Gsn^tm1Djk	involves: 129S4/SvJae * BALB/c	MGI:3628816
hm3	Gsn^tm1Djk/Gsn^tm1Djk	involves: 129S4/SvJae * C57BL/6	MGI:3628815
cx4	Capg^tm1Djk/Capg^tm1Djk Gsn^tm1Djk/Gsn^tm1Djk	involves: 129S4/SvJae	MGI:3842747

Genotype
MGI:2684175

hm1

• Allelic Composition: Gsn^tm1Djk/Gsn^tm1Djk
• Genetic Background: either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)

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

mortality/aging

premature death ( J:52545 )

• Background Sensitivity: not viable on either a "pure" BALB/c or C57BL/6 background

immune system

abnormal osteoclast differentiation ( J:60625 )

• podosomes not observed

• F-actin organized in web-like structures or is diffusely distributed

• osteopontin fails to cause an increase in F-actin organization into podosomes

increased leukocyte cell number ( J:24346 )

• increased total leukocyte count in peripheral blood

increased neutrophil cell number ( J:24346 )

• higher proportion of neutrophils in peripheral blood

abnormal immune system physiology ( J:24346 )

impaired neutrophil chemotaxis ( J:24346 )

• much slower neutrophil migration rates in chemotaxis tests

impaired neutrophil recruitment ( J:24346 )

• neutrophil recruitment to inflammatory sites half normal

abnormal osteoclast physiology ( J:60625 )

• reduced stimulation of osteoclast migration above basal levels

decreased inflammatory response ( J:24346 )

• neutrophile recruitment to inflammatory sites half normal

homeostasis/metabolism

abnormal platelet activation ( J:24346 )

• 13% higher resting actin filament content but F-actin levels are similar to controls after activation

increased bleeding time ( J:24346 )

• tail bleeding times 2x normal

• persistent, slow bleeding and re bleeding after initial cessation

abnormal wound healing ( J:24346 )

• dermal fibroblasts more active than controls in contracting collagen gels, embryonic fibroblasts slower

skeleton

abnormal skeleton morphology ( J:60625 )

abnormal osteoclast differentiation ( J:60625 )

• podosomes not observed

• F-actin organized in web-like structures or is diffusely distributed

• osteopontin fails to cause an increase in F-actin organization into podosomes

abnormal long bone diaphysis morphology ( J:60625 )

• increased diaphyseal thickness but no long bone deformities

abnormal long bone epiphyseal plate morphology ( J:60625 )

• chondrocytes of epiphyseal growth plates reduced in number and somewhat disorganized

• expanded matrix

increased compact bone thickness ( J:60625 )

• in tibial and femoral diaphysis at 14 weeks of age

osteopetrosis ( J:60625 )

• increased bone mass

abnormal skeleton physiology ( J:60625 )

abnormal bone remodeling ( J:60625 )

abnormal osteoclast physiology ( J:60625 )

• reduced stimulation of osteoclast migration above basal levels

hematopoietic system

abnormal osteoclast differentiation ( J:60625 )

• podosomes not observed

• F-actin organized in web-like structures or is diffusely distributed

• osteopontin fails to cause an increase in F-actin organization into podosomes

impaired neutrophil chemotaxis ( J:24346 )

• much slower neutrophil migration rates in chemotaxis tests

increased leukocyte cell number ( J:24346 )

• increased total leukocyte count in peripheral blood

increased neutrophil cell number ( J:24346 )

• higher proportion of neutrophils in peripheral blood

impaired neutrophil recruitment ( J:24346 )

• neutrophil recruitment to inflammatory sites half normal

abnormal osteoclast physiology ( J:60625 )

• reduced stimulation of osteoclast migration above basal levels

abnormal platelet activation ( J:24346 )

• 13% higher resting actin filament content but F-actin levels are similar to controls after activation

cellular

abnormal osteoclast differentiation ( J:60625 )

• podosomes not observed

• F-actin organized in web-like structures or is diffusely distributed

• osteopontin fails to cause an increase in F-actin organization into podosomes

impaired neutrophil chemotaxis ( J:24346 )

• much slower neutrophil migration rates in chemotaxis tests

Genotype
MGI:3628816

hm2

• Allelic Composition: Gsn^tm1Djk/Gsn^tm1Djk
• Genetic Background: involves: 129S4/SvJae * BALB/c

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:64868 )

• Background Sensitivity: after the N6 backcross to BALB/c, embryonic lethality is seen between E17.5 and birth; on a mixed 129Sv/BALB/c background, homozygotes survive

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:64868 )

♀ • ductal epithelial tree remains at 4 week stage in 8 week old mice

♀ • lack of terminal branching persists as long as the mice remain virgin

abnormal mammary gland growth during pregnancy ( J:64868 )

♀ • by mid gestation, mammary gland development is comparable to controls in early pregnancy

♀ • development continues but with delays

♀ • slower growth of mammary epithelium

♀ • mammary glands indistinguishable from controls during lactation

♀ • involution of mammary gland after weaning is normal

abnormal mammary duct terminal end bud morphology ( J:64868 )

♀ • Background Sensitivity: lack terminal end buds at 4 weeks of age but only seen when the genetic background is greater than 50% 129/Sv

reproductive system

abnormal mammary gland growth during pregnancy ( J:64868 )

♀ • by mid gestation, mammary gland development is comparable to controls in early pregnancy

♀ • development continues but with delays

♀ • slower growth of mammary epithelium

♀ • mammary glands indistinguishable from controls during lactation

♀ • involution of mammary gland after weaning is normal

integument

abnormal branching of the mammary ductal tree ( J:64868 )

♀ • ductal epithelial tree remains at 4 week stage in 8 week old mice

♀ • lack of terminal branching persists as long as the mice remain virgin

abnormal mammary gland growth during pregnancy ( J:64868 )

♀ • by mid gestation, mammary gland development is comparable to controls in early pregnancy

♀ • development continues but with delays

♀ • slower growth of mammary epithelium

♀ • mammary glands indistinguishable from controls during lactation

♀ • involution of mammary gland after weaning is normal

abnormal mammary duct terminal end bud morphology ( J:64868 )

♀ • Background Sensitivity: lack terminal end buds at 4 weeks of age but only seen when the genetic background is greater than 50% 129/Sv

Genotype
MGI:3628815

hm3

• Allelic Composition: Gsn^tm1Djk/Gsn^tm1Djk
• Genetic Background: involves: 129S4/SvJae * C57BL/6

nervous system

increased susceptibility to ischemic brain injury ( J:52545 )

• increased Ca+2 mediated proteolysis in ischemic brains

increased cerebral infarct size ( J:52545 )

• experimental brain ischemia leads to large infarct size

abnormal nervous system electrophysiology ( J:52545 )

• nerve depolarization results in increased Ca+2 in synaptosomes

cardiovascular system

abnormal pulmonary circulation ( J:94614 )

• vascular permeability to proteins increased in lungs

increased vascular permeability ( J:94614 )

• vascular permeability to proteins increased in lungs

• 18x increase in protein concentration in baseline lung lavage

• pulmonary artery ischemia causes slower increase in protein permeability than seen in controls

respiratory system

abnormal pulmonary circulation ( J:94614 )

• vascular permeability to proteins increased in lungs

homeostasis/metabolism

increased susceptibility to ischemic brain injury ( J:52545 )

• increased Ca+2 mediated proteolysis in ischemic brains

increased cerebral infarct size ( J:52545 )

• experimental brain ischemia leads to large infarct size

Genotype
MGI:3842747

cx4

• Allelic Composition: Capg^tm1Djk/Capg^tm1Djk; Gsn^tm1Djk/Gsn^tm1Djk
• Genetic Background: involves: 129S4/SvJae

immune system

abnormal macrophage physiology ( J:86517 )

• macrophages exhibit a decrease in spontaneous ruffling and do not show an increase in ruffling in response to macrophage colony stimulating factor (MCSF) as observed in wild-type; seen to a similar extent as in single Capg homozygotes

impaired macrophage phagocytosis ( J:86517 )

• macrophages exhibit a similar impairment of IgG, and complement-opsonized phagocytosis as seen in single Capg homozygotes

• macrophages exhibit a higher velocity of lanthanum-induced vesicle rocketing than seen in single Capg homozygotes

hematopoietic system

abnormal macrophage physiology ( J:86517 )

• macrophages exhibit a decrease in spontaneous ruffling and do not show an increase in ruffling in response to macrophage colony stimulating factor (MCSF) as observed in wild-type; seen to a similar extent as in single Capg homozygotes

impaired macrophage phagocytosis ( J:86517 )

• macrophages exhibit a similar impairment of IgG, and complement-opsonized phagocytosis as seen in single Capg homozygotes

• macrophages exhibit a higher velocity of lanthanum-induced vesicle rocketing than seen in single Capg homozygotes

cellular

impaired macrophage phagocytosis ( J:86517 )

• macrophages exhibit a similar impairment of IgG, and complement-opsonized phagocytosis as seen in single Capg homozygotes

• macrophages exhibit a higher velocity of lanthanum-induced vesicle rocketing than seen in single Capg homozygotes