Phenotypes associated with this allele

• Allele Symbol: Mbtps1^tm1Jdh
• Allele Name: targeted mutation 1, Jay D Horton
• Allele ID: MGI:2156484
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7281134
cn2	Mbtps1^tm1Jdh/Mbtps1^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7281135
cn3	Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Mx1-cre)29-4Her/0	involves: 129S6/SvEvTac * C57BL/6J * SJL	MGI:3846193
cn4	Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3846228

Genotype
MGI:7281134

cn1

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1^tm1Jdh; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1

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

cellular

increased chondrocyte apoptosis ( J:258274 )

• at P7 in the epiphyseal cartilage

growth/size/body

decreased body size ( J:258274 )

• dwarfed mice with fragile bones

hematopoietic system

abnormal bone marrow cell morphology/development ( J:258274 )

• decrease in the ability of bone marrow stem cells to form colony-forming unit-fibroblasts

• dramatic decrease in the number of mesenchymal-derived skeletal stem cells

skeleton

increased chondrocyte apoptosis ( J:258274 )

• at P7 in the epiphyseal cartilage

abnormal appendicular skeleton morphology ( J:258274 )

• smaller appendicular elements

abnormal axial skeleton morphology ( J:258274 )

• smaller axial elements

scoliosis ( J:258274 )

• varying degrees of scoliosis that can be severe and is seen as early as 7-10 days of age

decreased bone mineral density ( J:258274 )

• severe at P1 and P7

decreased volumetric bone mineral density ( J:258274 )

• in trabecular and cortical bone at P7

decreased compact bone volume ( J:258274 )

• decreased bone volume fraction at P7

decreased trabecular bone volume ( J:258274 )

• decrease in bone volume fraction

decreased compact bone thickness ( J:258274 )

• mid-diaphyseal cortical bone is smaller in width with thinner cortical bone

decreased osteoblast cell number ( J:258274 )

• decreased on the endosteal surface of the cortical bone

abnormal skeleton development ( J:258274 )

• at E15.5 and E16.5 in endochondral bone only cartilage is seen where the primary ossification center would normally be with no sign of vascular invasion

• dramatic decrease in the number of mesenchymal-derived skeletal stem cells in the bone marrow

decreased width of hypertrophic chondrocyte zone ( J:258274 )

• smaller

abnormal bone ossification ( J:258274 )

• osteogenic capacity of bone marrow stem cells is absent in vitro

decreased bone mineralization ( J:258274 )

• decrease in bone mineral apposition rate and bone formation rate/bone surface

delayed endochondral bone ossification ( J:258274 )

• at E15.5 and E16.5 only cartilage is seen where the primary ossification center would normally be with no sign of vascular invasion

• at P7 and P10, the secondary ossification center in the epiphyseal cartilage is absent

fragile skeleton ( J:258274 )

• drastic reduction in pMOI (a measure of resistance to torsional force)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic scoliosis		DOID:0060250		J:258274

Genotype
MGI:7281135

cn2

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1

growth/size/body

decreased body size ( J:258274 )

• heterozygous mice are smaller than wild-type or recombinase expressing controls but larger than homozygous mice

skeleton

abnormal appendicular skeleton morphology ( J:258274 )

• smaller appendicular elements, intermediate to homozygous mice

abnormal axial skeleton morphology ( J:258274 )

• smaller axial elements, intermediate to homozygous mice

abnormal compact bone thickness ( J:258274 )

• mid-diaphyseal cortical bone is smaller in width but not reduced in thickness

abnormal bone ossification ( J:258274 )

• osteogenic capacity of bone marrow stem cells is absent in vitro

Genotype
MGI:3846193

cn3

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1^tm1Jdh; Tg(Mx1-cre)29-4Her/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL

homeostasis/metabolism

abnormal lipid homeostasis ( J:72930 )

• following administration of pIpC, lipid synthesis is decrease compared to in similarly treated wild-type mice

abnormal intestinal lipid absorption ( J:72930 )

• following administration of pIpC, lipid clearance from the plasma is decreased compared to in similarly treated wild-type mice

decreased circulating cholesterol level ( J:72930 )

• decreased 36% following administration of pIpC

decreased circulating triglyceride level ( J:72930 )

• decreased 50% following administration of pIpC

decreased liver triglyceride level ( J:72930 )

• following administration of pIpC

digestive/alimentary system

abnormal intestinal lipid absorption ( J:72930 )

• following administration of pIpC, lipid clearance from the plasma is decreased compared to in similarly treated wild-type mice

liver/biliary system

decreased liver triglyceride level ( J:72930 )

• following administration of pIpC

Genotype
MGI:3846228

cn4

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1^tm1Jdh; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

Severe chondrodysplasia in Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Col2a1-cre)1Bhr/0 mice

mortality/aging

neonatal lethality, complete penetrance ( J:135374 )

• mice die during or shortly after birth

skeleton

abnormal skeleton morphology ( J:135374 )

• all skeletal elements are smaller than in wild-type mice

short basicranium ( J:135374 )

• the chondro-cranial base is shortened compared to in wild-type mice

small cranium ( J:135374 )

short mandible ( J:135374 )

short maxilla ( J:135374 )

abnormal skeleton development ( J:135374 )

• at E14.5, endochondral chondrocytes fail to exhibit a change from proliferation to hypertrophic cells unlike in wild-type mice

abnormal long bone hypertrophic chondrocyte zone ( J:135374 )

• at E15.5, mice lack an organized hypertrophic zone unlike wild-type mice

• differentiation of hypertrophic chonndrocytes is incomplete

• chondrocytes exhibit abnormal mineralization that precludes vascularization of skeletal elements

chondrodystrophy ( J:135374 )

abnormal skeleton physiology ( J:135374 )

• the skull bones exhibit increased sensitivity to potassium hydroxide compared to wild-type bones

abnormal bone mineralization ( J:135374 )

• mice exhibit abnomal mineralization of hypertrophic chondrocytes in long bones that is associated with increased chondrocyte apoptosis unlike in wild-type mice

failure of endochondral bone ossification ( J:135374 )

growth/size/body

protruding tongue ( J:135374 )

• mice are born with protruding tongues

decreased birth body size ( J:135374 )

• mice are small at birth

abnormal chest morphology ( J:135374 )

• the chest cavity is small and compresses the internal organs into the abdominal cavity unlike in wild-type mice

distended abdomen ( J:135374 )

craniofacial

short basicranium ( J:135374 )

• the chondro-cranial base is shortened compared to in wild-type mice

small cranium ( J:135374 )

short mandible ( J:135374 )

short maxilla ( J:135374 )

protruding tongue ( J:135374 )

• mice are born with protruding tongues

digestive/alimentary system

protruding tongue ( J:135374 )

• mice are born with protruding tongues

limbs/digits/tail

abnormal limb morphology ( J:135374 )

• the orientation of the limbs is skewed likely due to abnormal articular joint development