Phenotypes Associated with This Genotype

Genotype
MGI:3758814

• Allelic Composition: Comp^tm1Mbri/Comp^tm1Mbri
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

cellular

increased chondrocyte apoptosis ( J:125086 )

• the apoptosis rates for chondrocytes in the growth plate, proliferative zone and resting zone are increased by 3.3-fold, 12-fold and 2.5-fold, respectively, relative to apoptosis rates in wild-type mice

decreased chondrocyte proliferation ( J:125086 )

• proliferation of chondrocyte in the proliferative zone is decreased as indicated by a 24% reduction in bromodeoxyuridine-labelled chondrocytes relative to in wild-type mice

skeleton

increased chondrocyte apoptosis ( J:125086 )

• the apoptosis rates for chondrocytes in the growth plate, proliferative zone and resting zone are increased by 3.3-fold, 12-fold and 2.5-fold, respectively, relative to apoptosis rates in wild-type mice

decreased chondrocyte proliferation ( J:125086 )

• proliferation of chondrocyte in the proliferative zone is decreased as indicated by a 24% reduction in bromodeoxyuridine-labelled chondrocytes relative to in wild-type mice

osteoarthritis ( J:125086 )

• by 16 months, mice develop degenerative joint disease with loss of cartilage from the articular surface

abnormal hip joint morphology ( J:125086 )

• mice exhibit hip dysplasia characterized by the tuberosity of the ischium protruding from the pelvic region at an angle of greater than 15 degrees

short tibia ( J:125086 )

• by 9 weeks male mice tibia are 4% shorter than in wild-type mice

abnormal long bone epiphyseal plate proliferative zone ( J:125086 )

• chondrocytes alignment in the proliferative zone is disrupted from 2 weeks of age

• chondrocyte columns are reduced in number and in some cases terminate prematurely with a corresponding increase in the amount of space between individual columns

• at 3 weeks, proliferative zones are enlarged by greater than 15%

• chondrocytes within the proliferative zone are disorganized, irregularly shaped, heterogeneous and not aligned within the chondrons

• fibrillar material in the interterritorial matrix is more abundant and better defined than in heterozygotes and wild-type mice

abnormal ischium morphology ( J:125086 )

• mice exhibit hip dysplasia characterized by the tuberosity of the ischium protruding from the pelvic region at an angle of greater than 15 degrees

abnormal chondrocyte morphology ( J:125086 )

• chondrocytes exhibit a mild rough endoplasmic reticulum stress as determined by expression and activity levels of Hspa5, Eif2s1, Ddit3, Atf6, Casp12, and Bcl2

growth/size/body

decreased body weight ( J:125086 )

• by 9 weeks male mice are 6% lighter than wild-type mice and female mice are likewise lighter than wild-type mice

disproportionate dwarf ( J:125086 )

• by 9 weeks mice develop short limb dwarfism

immune system

osteoarthritis ( J:125086 )

• by 16 months, mice develop degenerative joint disease with loss of cartilage from the articular surface

limbs/digits/tail

abnormal hip joint morphology ( J:125086 )

• mice exhibit hip dysplasia characterized by the tuberosity of the ischium protruding from the pelvic region at an angle of greater than 15 degrees

short tibia ( J:125086 )

• by 9 weeks male mice tibia are 4% shorter than in wild-type mice

short limbs ( J:125086 )

• by 9 weeks mice develop short limb dwarfism

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pseudoachondroplasia		DOID:0080047	OMIM:177170	J:125086