Phenotypes associated with this allele

• Allele Symbol: Col2a1^tm1Dshh
• Allele Name: targeted mutation 1, Dongsheng Huang
• Allele ID: MGI:5620959
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Col2a1^tm1Dshh/Col2a1^tm1Dshh	involves: 129S6/SvEvTac * C57BL/6J	MGI:5688301
ht2	Col2a1^tm1Dshh/Col2a1^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:5688304

Genotype
MGI:5688301

hm1

• Allelic Composition: Col2a1^tm1Dshh/Col2a1^tm1Dshh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

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

mortality/aging

neonatal lethality, complete penetrance ( J:212712 )

• homozygotes die shortly after birth from respiratory distress

respiratory system

respiratory distress ( J:212712 )

• homozygotes die shortly after birth from respiratory distress

homeostasis/metabolism

cyanosis ( J:212712 )

• homozygotes appear cyanotic immediately after birth

growth/size/body

cleft palate ( J:212712 )

• homozygotes exhibit cleft palates

short snout ( J:212712 )

abnormal chest morphology ( J:212712 )

• homozygotes have hypoplastic thoraces

decreased body size ( J:212712 )

• neonatal homozygotes are dwarfed

• however, no differences are observed in the height and weight of fetuses (E16.5 and E18.5) or newborns

decreased body length ( J:212712 )

• homozygotes have shortened trunks

decreased fetal size ( J:212712 )

• at E16.5 and E18.5, mutant fetuses are smaller than wild-type

distended abdomen ( J:212712 )

• homozygotes exhibit distended abdomens

skeleton

abnormal cranium morphology ( J:212712 )

• homozygotes exhibit cranial bulges

short facial bone ( J:212712 )

• homozygotes exhibit truncated facial bones

abnormal phalanx morphology ( J:212712 )

• homozygotes display non-ossified middle phalanges

decreased length of long bones ( J:212712 )

• mutant long bones are shortened

short humerus ( J:212712 )

• mutant humeri are of normal size at E16.5, but significantly shorter at E18.5 and in newborns

short femur ( J:212712 )

• mutant femurs are of normal size at E16.5, but significantly shorter at E18.5 and in newborns

increased diameter of long bones ( J:212712 )

• mutant long bones are widened

abnormal scapula morphology ( J:212712 )

abnormal pelvic girdle bone morphology ( J:212712 )

• mutant pelvises appear shapeless

abnormal thoracic cage morphology ( J:212712 )

• mutant ribcages are malformed and the intercostal spaces are decreased

abnormal trabecular bone morphology ( J:212712 )

• at E19.5, trabecular bones are not formed properly due to misalignment of hypertrophic cells

abnormal chondrocyte morphology ( J:212712 )

• TEM analysis of mutant chondrocytes in the proliferating zone of E19.5 growth plates revealed that dilated vesicles, such as endoplasmic reticulum and Golgi bodies, are commonly observed

abnormal skeleton development ( J:212712 )

• at E16.5, homozygotes show severe defects in skeletal development that become more pronounced with growth

disorganized long bone epiphyseal plate ( J:212712 )

• at E19.5, H&E staining of the growth plates in proximal tibia revealed loss of the normal architecture

• toluidine blue and safranin O staining revealed that proteoglycans are severely reduced

• IHC analysis revealed that type II collagen and expression of Sox9 (which regulates the expression of type II collagen) in the growth plate were significantly decreased

• however, chondrocytes in the resting zone appear to be normally distributed

abnormal vertebrae development ( J:212712 )

• mutant vertebrae are less mineralized, shortened and widened

abnormal cartilage development ( J:212712 )

• TEM analysis revealed fewer collagen fibers and proteoglycan aggregates in mutant cartilage

• abnormal type II collagen is assembled into aberrant bundles

abnormal long bone epiphyseal plate proliferative zone ( J:212712 )

• at E19.5, mutant proliferating chondrocytes become fusiform, decreased in number, and aligned transversely and chaotically

• an EdU assay revealed significantly fewer proliferating chondrocytes in mutant growth pales

decreased width of hypertrophic chondrocyte zone ( J:212712 )

• at E19.5, the hypertrophic zone is lost; however, several hypertrophic chondrocytes can be detected at the boundary between the cartilage and the ossification zone

• although hypertrophic cells are barely generated, they express ~20% more type X collagen in the hypertrophic zone relative to wild-type controls

chondrodystrophy ( J:212712 )

• homozygotes exhibit early chondrocyte death due to severe ERS and activation of the ERS-UPR-apoptosis cascade; apoptosis occurs prior to hypertrophy, prevents the formation of a hypertrophic zone, impairs normal chondrogenic signaling pathways, and eventually causes disordered growth plates and chondrodysplasia

abnormal endochondral bone ossification ( J:212712 )

• homozygotes exhibit shortening of long bones suggesting that endochondral ossification is severely disturbed

delayed endochondral bone ossification ( J:212712 )

• endochondral ossification is slowed

• however, intramembranous ossification is normal

abnormal chondrocyte physiology ( J:212712 )

• misfolded procollagen is largely synthesized and retained in dilated endoplasmic reticulum and the endoplasmic reticulum stress (ERS)-unfolded protein response (UPR)-apoptosis cascade is activated

• proliferative chondrocytes undergo ERS-UPR-apoptosis before they can differentiate into hypertrophic cells

limbs/digits/tail

abnormal phalanx morphology ( J:212712 )

• homozygotes display non-ossified middle phalanges

short humerus ( J:212712 )

• mutant humeri are of normal size at E16.5, but significantly shorter at E18.5 and in newborns

short femur ( J:212712 )

• mutant femurs are of normal size at E16.5, but significantly shorter at E18.5 and in newborns

short limbs ( J:212712 )

• homozygotes have shortened limbs

craniofacial

abnormal cranium morphology ( J:212712 )

• homozygotes exhibit cranial bulges

short facial bone ( J:212712 )

• homozygotes exhibit truncated facial bones

cleft palate ( J:212712 )

• homozygotes exhibit cleft palates

short snout ( J:212712 )

digestive/alimentary system

cleft palate ( J:212712 )

• homozygotes exhibit cleft palates

Genotype
MGI:5688304

ht2

• Allelic Composition: Col2a1^tm1Dshh/Col2a1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:212712 )

• heterozygotes are viable and overtly normal with no detectable defects in skeletal development

• expression of several endoplasmic reticulum stress (ERS)-related genes is partly increased in chondrocytes, indicating limited ERS; however, ERS-unfolded protein response (UPR)-apoptosis is avoided such that normal growth plate structure and endochondral ossification process are preserved