Phenotypes associated with this allele

• Allele Symbol: Tg(Gdf5-cre,-ALPP)1Kng
• Allele Name: transgene insertion 1, David M Kingsley
• Allele ID: MGI:3577961
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr Tg(Gdf5-cre,-ALPP)1Kng/0	involves: 129 * C57BL/6 * FVB/N-Tg(Gdf5-cre-ALPP)1Kng	MGI:3578783
cn2	Ank^tm1Kng/Ank^+ Tg(Gdf5-cre,-ALPP)1Kng/?	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3715341
cn3	Erg^tm1.1Iwamo/Erg^tm1.1Iwamo Tg(Gdf5-cre,-ALPP)1Kng/?	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:5910547

Genotype
MGI:3578783

cn1

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr; Tg(Gdf5-cre,-ALPP)1Kng/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N-Tg(Gdf5-cre-ALPP)1Kng

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

Joint defects in Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.2Bhr Tg(Gdf5-cre,-ALPP)1Kng/0 mice

skeleton

osteoarthritis ( J:97780 )

• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints

• deterioration similar to that in the foot is also seen in the knee

osteosclerosis ( J:97780 )

• at 7 weeks and 9 months, subchondral sclerosis is seen, especially in the epiphysis of the femur

abnormal articular cartilage morphology ( J:97780 )

• many joints, including those in the foot and the knee, showed a decrease in cartilage however cartilage was normal in non-articular regions

• cartilage formation is reduced and cells with a noncartilaginous appearance are seen in the fibrocartilaginous meniscus that sits between the femur and tibia

abnormal synovial joint membrane morphology ( J:97780 )

• hypertrophy of the synovial membrane is seen in some joints, particulary in the ankle region

• in severely affected joints the synovial membrane grows into the joint space and this is associated with articular cartilage loss

• synovial hypertophy decreases with age

fused joints ( J:97780 )

• at some sites in the ankles the joints appear to be absent and bones that are normally separated are fused

• in all mutants the second distal tarsal was fused to the central tarsal bone

abnormal skeleton development ( J:97780 )

• E15.5 expression of early joint markers is decreased in the ankle suggesting the fusion of some of the ankle joints is a result of incomplete segmentation

abnormal long bone epiphysis morphology ( J:97780 )

• at 7 weeks and 9 months, the domed epiphysis of the tibia is flattened and depressed

abnormal cartilage development ( J:97780 )

• accelerated cartilage maturation is seen

decreased joint mobility ( J:97780 )

• the range of motion of the digit joints is reduced

behavior/neurological

decreased grip strength ( J:97780 )

• the ability to grasp and remain suspended from a slender rod is significantly reduced

hearing/vestibular/ear

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

limbs/digits/tail

syndactyly ( J:97780 )

• soft tissue syndactyly is seen involving the first and second digits that is more severe and more frequent in the forefeet compared to the hindfeet (incidence of 91% and 50%, respectively)

• decreased apoptosis is seen at E14.5 between the first and second digits and in the posterior margin of the fifth digit

immune system

osteoarthritis ( J:97780 )

• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints

• deterioration similar to that in the foot is also seen in the knee

craniofacial

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

growth/size/body

abnormal ear shape ( J:97780 )

• the ears are shorter and often lay flatter against the head

short ears ( J:97780 )

• the ears are shorter than normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:97780

Genotype
MGI:3715341

cn2

• Allelic Composition: Ank^tm1Kng/Ank⁺; Tg(Gdf5-cre,-ALPP)1Kng/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

skeleton

abnormal cementum morphology ( J:122727 )

• expanded layer of cementum

abnormal joint morphology ( J:122727 )

• 64 of 84 mutants have abnormal joints

• ectopic cartilage depositions occurs similar to in Ank^tm1.1Kng homozygotes

• ectopic mineral deposition in joints

abnormal articular cartilage morphology ( J:122727 )

• articular cartilage of joints is disrupted

fused joints ( J:122727 )

• ankylosis, however joint fusion is delayed compared to Ank^ank or Ank^tm1.1Kng homozygotes

decreased joint mobility ( J:122727 )

• at 9 weeks, mice develop decreased mobility in the distal joints

craniofacial

abnormal cementum morphology ( J:122727 )

• expanded layer of cementum

growth/size/body

abnormal cementum morphology ( J:122727 )

• expanded layer of cementum

Genotype
MGI:5910547

cn3

• Allelic Composition: Erg^tm1.1Iwamo/Erg^tm1.1Iwamo; Tg(Gdf5-cre,-ALPP)1Kng/?
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * FVB/N

skeleton

increased susceptibility to induced arthritis ( J:243715 )

• 8 week old mice are more susceptible to surgically induced osteoarthritis in knees than controls

• 4 weeks post-surgery articular cartilage is eroded and the region develops ectopic chondrocyte hypertrophy and is lacking Safranin O-staining proteoglycans and lubricin

osteoarthritis ( J:243715 )

• knee articular cartilage is thin, eroded and almost absent in joints of 6-7 month old mice

• tibial plateau exhibits arthritic changes based on osteoarthritis assessment criteria

• knee joint surface of the femur exhibits arthritic changes based on osteoarthritis assessment criteria

abnormal articular cartilage morphology ( J:243715 )

• knee articular cartilage is thin, eroded and almost absent in joints of 6-7 month old mice

immune system

increased susceptibility to induced arthritis ( J:243715 )

• 8 week old mice are more susceptible to surgically induced osteoarthritis in knees than controls

• 4 weeks post-surgery articular cartilage is eroded and the region develops ectopic chondrocyte hypertrophy and is lacking Safranin O-staining proteoglycans and lubricin

osteoarthritis ( J:243715 )

• knee articular cartilage is thin, eroded and almost absent in joints of 6-7 month old mice

• tibial plateau exhibits arthritic changes based on osteoarthritis assessment criteria

• knee joint surface of the femur exhibits arthritic changes based on osteoarthritis assessment criteria

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:243715