Phenotypes associated with this allele

• Allele Symbol: Clec11a^em1Sjm
• Allele Name: endonuclease-mediated mutation 1, Sean Morrison
• Allele ID: MGI:5888865
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Clec11a^em1Sjm/Clec11a^em1Sjm	involves: C57BL/6 * C57BL/Ka	MGI:5897274

Genotype
MGI:5897274

hm1

• Allelic Composition: Clec11a^em1Sjm/Clec11a^em1Sjm
• Genetic Background: involves: C57BL/6 * C57BL/Ka

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

skeleton

impaired osteoblast differentiation ( J:239391 )

• under osteogenic culture conditions, bone marrow stromal cells from femur bone marrow form significantly fewer osteoblasts with significantly lower expression of mature osteoblast markers than control cells

abnormal bone healing ( J:239391 )

• at 2 weeks after mid-diaphyseal femur fracture, mice show significantly less callus bone around the fracture site and more callus cartilage than controls, suggesting delayed endochondral ossification

• microCT analysis of the callus at the fracture site revealed significantly reduced trabecular bone volume, trabecular number, trabecular thickness, and trabecular connectivity density and significantly increased trabecular spacing but normal bone mineral density relative to controls

• callus volume, callus diameter, and polar moment of inertia are significantly increased, suggesting impaired fracture healing

decreased femur compact bone thickness ( J:239391 )

• cortical bone area, cortical area/total area ratio, and cortical thickness in the femur diaphysis are significantly reduced at 16 months but not at 2 or 10 months of age

short femur ( J:239391 )

• femur length is slightly but significantly reduced in 2, 10 and 16 months of age

decreased bone mineral density of femur ( J:239391 )

• bone mineral density in the distal femur metaphysis is significantly reduced at 2 months, with no further reductions noted at 10 and 16 months of age

decreased trabecular bone volume ( J:239391 )

• trabecular bone volume in the distal femur metaphysis is reduced by ~24% at 2 months and by ~62% and ~64% at 10 and 16 months of age, respectively

• trabecular bone volume is significantly reduced in the L3 vertebral body at 2, 10, and 16 months of age

• following daily s.c. injections of 50 mg/kg recombinant Clec11a to 6-month-old for 28 days, trabecular bone volume in the distal femur metaphysis is restored to control levels

decreased bone trabecula number ( J:239391 )

• trabecular number in the distal femur metaphysis is significantly reduced at 10 and 16 months, but not at 2 months, of age

• trabecular number is significantly reduced in L3 vertebrae at 2, 10, and 16 months of age

• following daily s.c. injections of 50 mg/kg recombinant Clec11a to 6-month-old for 28 days, trabecular number in the distal femur metaphysis is restored to control levels

increased bone trabecular spacing ( J:239391 )

• trabecular spacing in the distal femur metaphysis is significantly increased at 2 months of age, with more severe increases noted at 10 and 16 months of age

• trabecular spacing is significantly increased in L3 vertebrae at 2, 10, and 16 months of age

• following daily s.c. injections of 50 mg/kg recombinant Clec11a to 6-month-old for 28 days, trabecular spacing in the distal femur metaphysis is restored to control levels

decreased trabecular bone connectivity density ( J:239391 )

• trabecular bone connectivity density in the distal femur metaphysis is significantly reduced at 10 months, with a more severe reduction noted at 16 months of age

• following daily s.c. injections of 50 mg/kg recombinant Clec11a to 6-month-old for 28 days, trabecular connectivity density is restored to control levels

decreased trabecular bone thickness ( J:239391 )

• trabecular bone thickness in the distal femur metaphysis is significantly reduced at 2 months, with more severe reductions noted at 10 and 16 months of age

• following daily s.c. injections of 50 mg/kg recombinant Clec11a to 6-month-old for 28 days, trabecular thickness is restored to control levels

decreased bone mineralization ( J:239391 )

• trabecular bone mineral apposition rate is significantly decreased in the distal femur metaphysis at 2 and 10 months of age

delayed endochondral bone ossification ( J:239391 )

• at 2 weeks after mid-diaphyseal femur fracture, mice show significantly less callus bone around the fracture site and more callus cartilage than controls, suggesting delayed endochondral ossification

decreased bone ossification ( J:239391 )

• trabecular bone formation rate is significantly decreased in the distal femur metaphysis at 2 and 10 months of age

• however, bone resorption is normal, as measured by the deoxypyridinoline/creatinine ratio in urine

decreased bone strength ( J:239391 )

decreased femur maximal load ( J:239391 )

• peak load is significantly reduced in the femur diaphysis at 2, 10, and 16 months of age

• however, yield load is normal at all ages tested

decreased energy dissipated prior to femur fracture ( J:239391 )

• fracture energy is significantly reduced in the femur diaphysis at 2, 10, and 16 months of age

homeostasis/metabolism

abnormal bone healing ( J:239391 )

• at 2 weeks after mid-diaphyseal femur fracture, mice show significantly less callus bone around the fracture site and more callus cartilage than controls, suggesting delayed endochondral ossification

• microCT analysis of the callus at the fracture site revealed significantly reduced trabecular bone volume, trabecular number, trabecular thickness, and trabecular connectivity density and significantly increased trabecular spacing but normal bone mineral density relative to controls

• callus volume, callus diameter, and polar moment of inertia are significantly increased, suggesting impaired fracture healing

hematopoietic system

hematopoietic system phenotype ( J:239391 )

N • adult mice are grossly normal and exhibit normal hematopoiesis

abnormal bone marrow cell morphology/development ( J:239391 )

• under osteogenic culture conditions, bone marrow stromal cells from femur bone marrow give rise to significantly fewer cells with alkaline phosphatase (a marker of mature osteoblasts and pre-adipocytes) or alizarin red (a marker of mineralization by mature osteoblasts) staining relative to control cells, indicating impaired differentiation of bone marrow mesenchymal progenitors into mature osteoblasts

• addition of recombinant Clec11a rescues osteogenesis by bone marrow stromal cells at 7 and 14 days after induction of differentiation

• in culture adipogenic and chondrogenic differentiation of bone marrow stromal cells is normal, as shown by Oil Red O and Toluidine blue staining

adipose tissue

abnormal fat cell morphology ( J:239391 )

• mice show significantly more Perilipin+ adipocytes in femur sections through the bone marrow metaphysis at 10 but not at 2 months of age relative to controls

• in contrast, number of Safranin O+ chondrocytes is not significantly altered in femur sections at 2 or 10 months of age

limbs/digits/tail

decreased femur compact bone thickness ( J:239391 )

• cortical bone area, cortical area/total area ratio, and cortical thickness in the femur diaphysis are significantly reduced at 16 months but not at 2 or 10 months of age

short femur ( J:239391 )

• femur length is slightly but significantly reduced in 2, 10 and 16 months of age

cellular

impaired osteoblast differentiation ( J:239391 )

• under osteogenic culture conditions, bone marrow stromal cells from femur bone marrow form significantly fewer osteoblasts with significantly lower expression of mature osteoblast markers than control cells