Phenotypes Associated with This Genotype

Genotype
MGI:3653631

• Allelic Composition: Tnfrsf11b^tm1Khs/Tnfrsf11b^tm1Khs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:48325 )

• at weaning only 18.7% are homozygous rather than the expected 25%

growth/size/body

postnatal growth retardation ( J:48325 )

skeleton

abnormal middle ear ossicle morphology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) and thinning are seen in all three middle ear ossicles

abnormal incus body morphology ( J:111153 )

• thinning, particularly of the incus body

abnormal malleus morphology ( J:111153 )

• thinning, particularly in the manubrium and processus brevis

• malleal cortical thickness is significantly reduced

abnormal stapes morphology ( J:111153 )

• thinning, particularly of the arch

abnormal stapes annular ligament morphology ( J:111153 )

• the ligament between the stapedial footplate and the otic capsule is replaced with a bony tissue resulting in fusion of the stapes to the otic capsule

abnormal stapes footplate morphology ( J:111153 )

• the stapes footplate is thinner and broader at the periphery

abnormal bone structure ( J:111153 )

increased osteoclast cell number ( J:80503 )

• increased numbers in the metaphyseal region

decreased bone mineral density ( J:48325 , J:111153 )

• reduced radiodensity especially in the tail and the distal portions of the femur and tibia (J:48325)

• bone mineral density is reduced by 27.5% compared to wild-type (J:48325)

• tibial cortical bone mineral density is reduced (J:111153)

abnormal trabecular bone morphology ( J:48325 )

• absent from the femur

• at 8 weeks of age trabecular bone is poorly extended

osteoporosis ( J:48325 )

abnormal skeleton development ( J:111153 )

abnormal osteoclast differentiation ( J:48325 , J:111153 )

• at 8 weeks of age, osteoclasts are seen throughout the trabecular and cortical bone, including in the chondro-osseous junction and the intertrabecular areas of the trabecular bone (J:48325)

• at 13 weeks of age, osteoclasts are seen in the growth plate (J:48325)

• increase in the number of tartrate-resistant acid phosphatase positive multinucleated cells in the mallei (J:111153)

abnormal long bone epiphyseal plate morphology ( J:48325 )

• at 8 and 13 weeks, but not 5 weeks, progressive destruction of the growth plate is seen

abnormal skeleton physiology ( J:111153 )

abnormal osteoclast physiology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) in all three middle ear ossicles and in the otic capsule

fragile skeleton ( J:48325 )

• spontaneous fractures of the tibia or femur

• at 8 weeks of age trabecular bone is poorly extended

hearing/vestibular/ear

abnormal inner ear morphology ( J:111153 )

• the ligament between the stapedial footplate and the otic capsule is replaced with a bony tissue resulting in fusion of the stapes to the otic capsule

abnormal middle ear morphology ( J:111153 )

• junction between the stapes and the oval window of the cochlea is tighter

abnormal middle ear ossicle morphology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) and thinning are seen in all three middle ear ossicles

abnormal incus body morphology ( J:111153 )

• thinning, particularly of the incus body

abnormal malleus morphology ( J:111153 )

• thinning, particularly in the manubrium and processus brevis

• malleal cortical thickness is significantly reduced

abnormal stapes morphology ( J:111153 )

• thinning, particularly of the arch

abnormal stapes annular ligament morphology ( J:111153 )

• the ligament between the stapedial footplate and the otic capsule is replaced with a bony tissue resulting in fusion of the stapes to the otic capsule

abnormal stapes footplate morphology ( J:111153 )

• the stapes footplate is thinner and broader at the periphery

increased or absent threshold for auditory brainstem response ( J:111153 )

• starting at 10 weeks of age, progressive increase in auditory brain-stem response thresholds is seen; however, no difference is seen at 6 weeks of age

• at 15 weeks of age thresholds are 20 dB higher at 20 kHz compared to wild-type mice

craniofacial

abnormal middle ear ossicle morphology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) and thinning are seen in all three middle ear ossicles

abnormal incus body morphology ( J:111153 )

• thinning, particularly of the incus body

abnormal malleus morphology ( J:111153 )

• thinning, particularly in the manubrium and processus brevis

• malleal cortical thickness is significantly reduced

abnormal stapes morphology ( J:111153 )

• thinning, particularly of the arch

abnormal stapes annular ligament morphology ( J:111153 )

• the ligament between the stapedial footplate and the otic capsule is replaced with a bony tissue resulting in fusion of the stapes to the otic capsule

abnormal stapes footplate morphology ( J:111153 )

• the stapes footplate is thinner and broader at the periphery

hematopoietic system

abnormal osteoclast differentiation ( J:48325 , J:111153 )

• at 8 weeks of age, osteoclasts are seen throughout the trabecular and cortical bone, including in the chondro-osseous junction and the intertrabecular areas of the trabecular bone (J:48325)

• at 13 weeks of age, osteoclasts are seen in the growth plate (J:48325)

• increase in the number of tartrate-resistant acid phosphatase positive multinucleated cells in the mallei (J:111153)

increased osteoclast cell number ( J:80503 )

• increased numbers in the metaphyseal region

abnormal osteoclast physiology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) in all three middle ear ossicles and in the otic capsule

immune system

abnormal osteoclast differentiation ( J:48325 , J:111153 )

• at 8 weeks of age, osteoclasts are seen throughout the trabecular and cortical bone, including in the chondro-osseous junction and the intertrabecular areas of the trabecular bone (J:48325)

• at 13 weeks of age, osteoclasts are seen in the growth plate (J:48325)

• increase in the number of tartrate-resistant acid phosphatase positive multinucleated cells in the mallei (J:111153)

increased osteoclast cell number ( J:80503 )

• increased numbers in the metaphyseal region

abnormal osteoclast physiology ( J:111153 )

• increase in tartrate-resistant acid phosphatase activity (marker of osteoclasts and resorption lacunae) in all three middle ear ossicles and in the otic capsule

cellular

abnormal osteoclast differentiation ( J:48325 , J:111153 )

• at 8 weeks of age, osteoclasts are seen throughout the trabecular and cortical bone, including in the chondro-osseous junction and the intertrabecular areas of the trabecular bone (J:48325)

• at 13 weeks of age, osteoclasts are seen in the growth plate (J:48325)

• increase in the number of tartrate-resistant acid phosphatase positive multinucleated cells in the mallei (J:111153)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoporosis		DOID:11476	OMIM:166710	J:48325