Phenotypes Associated with This Genotype

Genotype
MGI:5428021

• Allelic Composition: Fam20c^tm1.1Cqi/Fam20c^tm1.1Cqi; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

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

Small size, flat face, hypomineralization, and distorted spine in Fam20c^tm1.1Cqi/Fam20c^tm1.1Cqi Edil3^{Tg(Sox2-cre)1Amc}/0 mice

reproductive system

female infertility ( J:185208 )

♀

male infertility ( J:185208 )

♂

skeleton

decreased chondrocyte apoptosis ( J:185208 )

• decrease in the percentage of apoptotic cells in the hypertrophic zone

decreased chondrocyte proliferation ( J:185208 )

• decrease in the absolute number of proliferating chondrocytes

abnormal skeleton morphology ( J:185208 )

• small skeleton

impaired osteoblast differentiation ( J:185208 )

• downregulation of markers of terminal differentiation at 3 weeks of age

small cranium ( J:185208 )

• at 1 week of age

abnormal limb long bone morphology ( J:185208 )

• appearance of more porous areas in both the outer and inner bone surfaces

abnormal long bone diaphysis morphology ( J:185208 )

• increase in porosity

• the diaphysis region of the tibia has more osteoid/hypomineralized areas in the cortical bone

abnormal long bone epiphyseal plate morphology ( J:185208 )

• malformed

abnormal long bone epiphyseal plate proliferative zone ( J:185208 )

• reduced in size

• decrease in the absolute number of proliferating chondrocytes

increased width of hypertrophic chondrocyte zone ( J:185208 )

abnormal vertebral column morphology ( J:185208 )

• distorted spine

decreased bone mineral density ( J:185208 )

• at 6 weeks of age

• significantly lower mineral Apparent Density and Material Density in the tibia midshaft region at 3 and 6 weeks of age

decreased compact bone thickness ( J:185208 )

abnormal osteocyte morphology ( J:185208 )

• appear immature

abnormal chondrocyte differentiation ( J:185208 )

• both early stage differentiation and late stage maturation are affected

decreased bone mineralization ( J:185208 )

• lower levels of mineralization at 5 months of age

• significantly lower mineral deposition rate

osteomalacia ( J:185208 )

rickets ( J:185208 )

• hypophosphatemic rickets

delayed bone ossification ( J:185208 )

• in the ribs, long bones, and carpus at 1 weeks of age

delayed endochondral bone ossification ( J:185208 )

• delay in secondary ossification centers in the epiphysis in the long bones and vertebrae at 6 weeks of age

delayed cranial suture closure ( J:185208 )

fragile skeleton ( J:185208 )

• multiple fractures are often seen after 3 weeks of age

craniofacial

small cranium ( J:185208 )

• at 1 week of age

flat face ( J:185208 )

short snout ( J:185208 )

growth/size/body

flat face ( J:185208 )

short snout ( J:185208 )

decreased body size ( J:185208 )

• smaller stature at 1 week of age

• prominent dwarfism at 4 weeks of age

decreased body weight ( J:185208 )

postnatal growth retardation ( J:185208 )

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:185208 )

• at 18 and 42 days of age

decreased circulating phosphate level ( J:185208 )

• at 18 and 42 days of age

abnormal circulating protein level ( J:185208 )

• increase in serum FGF23 levels at 18 and 42 days of age

abnormal vitamin D level ( J:185208 )

• the 1,25(OH)2D3 level is reduced at 18 days of age but not at 42 days of age

limbs/digits/tail

abnormal limb long bone morphology ( J:185208 )

• appearance of more porous areas in both the outer and inner bone surfaces

cellular

decreased chondrocyte apoptosis ( J:185208 )

• decrease in the percentage of apoptotic cells in the hypertrophic zone

impaired osteoblast differentiation ( J:185208 )

• downregulation of markers of terminal differentiation at 3 weeks of age

decreased chondrocyte proliferation ( J:185208 )

• decrease in the absolute number of proliferating chondrocytes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rickets		DOID:10609		J:185208