Phenotypes associated with this allele

• Allele Symbol: Traf6^tm1Mak
• Allele Name: targeted mutation 1, Tak Mak
• Allele ID: MGI:1859953
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Traf6^tm1Mak/Traf6^tm1Mak	involves: 129P3/J	MGI:2655556

Genotype
MGI:2655556

hm1

• Allelic Composition: Traf6^tm1Mak/Traf6^tm1Mak
• Genetic Background: involves: 129P3/J

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

mortality/aging

decreased survivor rate ( J:54467 )

• only a few homozygotes survive past 2 weeks of age

perinatal lethality, incomplete penetrance ( J:54467 )

• a portion of homozygotes die between E17.5 and birth

postnatal lethality, incomplete penetrance ( J:54467 )

• most homozygotes that survive the perinatal period appear normal at birth but fail to thrive and die within 2 weeks of life

• only 11% (instead of expected 25%) are genotyped as homozygotes at 2 weeks of age

growth/size/body

enlarged heart ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 1.3-fold increase in heart size

absent incisors ( J:54467 )

• no incisors are detected in the oral cavity at 4 weeks of age

absent molars ( J:54467 )

• no molars are detected in the oral cavity at 4 weeks of age

failure of tooth eruption ( J:54467 )

• all homozygotes display failure of molar and incisor eruption

decreased body weight ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 20%-30% reduction in body mass relative to control littermates

decreased body length ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 20%-30% reduction in body length relative to control littermates

enlarged liver ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 1.3-fold increase in liver size

enlarged spleen ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 2- to 6-fold increase in spleen size

craniofacial

absent incisors ( J:54467 )

• no incisors are detected in the oral cavity at 4 weeks of age

absent molars ( J:54467 )

• no molars are detected in the oral cavity at 4 weeks of age

failure of tooth eruption ( J:54467 )

• all homozygotes display failure of molar and incisor eruption

skeleton

absent incisors ( J:54467 )

• no incisors are detected in the oral cavity at 4 weeks of age

absent molars ( J:54467 )

• no molars are detected in the oral cavity at 4 weeks of age

failure of tooth eruption ( J:54467 )

• all homozygotes display failure of molar and incisor eruption

abnormal osteoclast morphology ( J:54467 )

• unlike wild-type osteoclasts which are attached to the bone, most mutant osteoclasts are withdrawn from the bone surface

• however, the number of mutant TRAP⁺ osteoclasts per mm² tissue area is not significantly altered relative to that in control littermates

abnormal osteoclast physiology ( J:54467 )

• although a few mutant osteoclasts are shown to form structures that resemble attachment zones and disorganized ruffled borders, they appear unable to resorb bone properly, suggesting a defect in osteoclast function

abnormal long bone morphology ( J:54467 )

• at 4 weeks of age, mutant long bones show a distinct broadening at the ends due to a failure in bone modeling

abnormal long bone metaphysis morphology ( J:54467 )

• at 4 weeks of age, long bone metaphyses are enlarged

decreased length of long bones ( J:54467 )

• at 4 weeks of age, mutant long bones, esp. the femur, are reduced in length

short femur ( J:54467 )

increased bone mineral density ( J:54467 )

• at 4 weeks of age, homozygotes display an increase in total and trabecular bone mineral density relative to control littermates

osteopetrosis ( J:54467 )

• surviving homozygotes are severely osteopetrotic and display radio-opaque long bones and vertebral bodies

• in contrast to long bones, bones that develop by intramembranous formation (e.g. skull) appear radiographically normal

decreased bone resorption ( J:54467 )

• at 4 weeks of age, the shaft of mutant femurs is filled with hypertrophic cartilage and bony trabeculae, indicating failed bone resorption

• however, there is some evidence of periosteal bone modeling occurring adjacent to the growth plates

immune system

decreased B cell proliferation ( J:54467 )

• in vitro, mutant splenic B cells fail to proliferate in response to stimulation with an agonistic rat anti-mouse CD40 mAb, indicating a defect in CD40 signaling

• surprisingly, mutant splenic B cells also fail to proliferate in response to LPS stimulation

enlarged spleen ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 2- to 6-fold increase in spleen size

abnormal osteoclast morphology ( J:54467 )

• unlike wild-type osteoclasts which are attached to the bone, most mutant osteoclasts are withdrawn from the bone surface

• however, the number of mutant TRAP⁺ osteoclasts per mm² tissue area is not significantly altered relative to that in control littermates

abnormal macrophage physiology ( J:54467 )

• in vitro, mutant thioglycollate-elicited peritoneal macrophages are impaired in their ability to activate NOS2 (inducible nitric oxide synthase-2; iNOS) in response to IL-1beta plus IFN-gamma, but respond like wild type cells to TNF plus IFN-gamma, indicating a defect in IL-1 signaling

• in addition, mutant naive bone marrow macrophages are impaired in their ability to induce iNOS in response to LPS (even at a high LPS dose of 10⁴ ng/ml), but respond like wild type cells to TNF plus IFN-gamma, indicating a defect in LPS signaling

abnormal osteoclast physiology ( J:54467 )

• although a few mutant osteoclasts are shown to form structures that resemble attachment zones and disorganized ruffled borders, they appear unable to resorb bone properly, suggesting a defect in osteoclast function

decreased tumor necrosis factor secretion ( J:54467 )

• mutant peripheral blood leukocytes are impaired in their ability to secrete TNF in response to LPS treatment

hematopoietic system

decreased B cell proliferation ( J:54467 )

• in vitro, mutant splenic B cells fail to proliferate in response to stimulation with an agonistic rat anti-mouse CD40 mAb, indicating a defect in CD40 signaling

• surprisingly, mutant splenic B cells also fail to proliferate in response to LPS stimulation

enlarged spleen ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 2- to 6-fold increase in spleen size

hypochromic anemia ( J:54467 )

• homozygotes surviving past 2 weeks of age display moderate normocytic, hypochromic anemia

abnormal osteoclast morphology ( J:54467 )

• unlike wild-type osteoclasts which are attached to the bone, most mutant osteoclasts are withdrawn from the bone surface

• however, the number of mutant TRAP⁺ osteoclasts per mm² tissue area is not significantly altered relative to that in control littermates

abnormal macrophage physiology ( J:54467 )

• in vitro, mutant thioglycollate-elicited peritoneal macrophages are impaired in their ability to activate NOS2 (inducible nitric oxide synthase-2; iNOS) in response to IL-1beta plus IFN-gamma, but respond like wild type cells to TNF plus IFN-gamma, indicating a defect in IL-1 signaling

• in addition, mutant naive bone marrow macrophages are impaired in their ability to induce iNOS in response to LPS (even at a high LPS dose of 10⁴ ng/ml), but respond like wild type cells to TNF plus IFN-gamma, indicating a defect in LPS signaling

abnormal osteoclast physiology ( J:54467 )

• although a few mutant osteoclasts are shown to form structures that resemble attachment zones and disorganized ruffled borders, they appear unable to resorb bone properly, suggesting a defect in osteoclast function

cardiovascular system

enlarged heart ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 1.3-fold increase in heart size

liver/biliary system

enlarged liver ( J:54467 )

• homozygotes surviving past 2 weeks of age display a 1.3-fold increase in liver size

limbs/digits/tail

short femur ( J:54467 )

homeostasis/metabolism

decreased circulating phosphate level ( J:54467 )

• homozygotes exhibit reduced serum phosphate levels relative to control littermates

• in contrast, serum calcium levels remain unaffected

cellular

decreased B cell proliferation ( J:54467 )

• in vitro, mutant splenic B cells fail to proliferate in response to stimulation with an agonistic rat anti-mouse CD40 mAb, indicating a defect in CD40 signaling

• surprisingly, mutant splenic B cells also fail to proliferate in response to LPS stimulation