Phenotypes Associated with This Genotype

Genotype
MGI:8275713

• Allelic Composition: Recql4^tm1.1Brle/Recql4^tm1.1Brle; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * SJL/J

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:309253 )

• about 1/3 of mice die before weaning age, most likely due to difficulty feeding as a result of limb defects

growth/size/body

postnatal growth retardation ( J:309253 )

limbs/digits/tail

abnormal limb morphology ( J:309253 )

• mice that survive show smaller limbs at 3 weeks of age

adactyly ( J:309253 )

• missing digits or decreased mineralization in the remaining phalanges are commonly seen

abnormal forelimb morphology ( J:309253 )

• P0 pups show severely foreshortened and deformed forelimbs

short forelimb ( J:309253 )

• P0 pups show severely foreshortened forelimbs

abnormal hindlimb morphology ( J:309253 )

• hindlimbs are less affected than forelimbs but are smaller and shorter

short hindlimb ( J:309253 )

abnormal limb development ( J:309253 )

• embryos start to show limb defects at E12.5 and mice show severe limb developmental defects at birth

skeleton

abnormal long bone epiphyseal plate morphology ( J:309253 )

• at E18.5, distal femur growth plates show reduced cell density of chondrocytes and increased cell size in the resting zone, proliferating zone, and hypertrophic zone

• at 3 weeks of age, mice show disorganized distal femur growth plates and abnormal chondrocyte morphology showing increased cell size

abnormal long bone epiphyseal plate proliferative zone ( J:309253 )

• E18.5 growth plates show reduced number of BrdU+ cells in the proliferating zone indicating decreased cell proliferation

abnormal chondrocyte morphology ( J:309253 )

• growth plate chondrocytes exhibit increased cell size in the resting zone, proliferating zone, and hypertrophic zone

abnormal bone ossification ( J:309253 )

• mice that survive show abnormal ossification in the joint region of the hindlimbs at 3 weeks of age

• however, formation of primary ossification centers of long bones at E13.5 appears normal

premature coronal suture closure ( J:309253 )

• skulls show bilateral coronal suture synostoses at birth and synostoses of the coronal sutures are seen in 3-week-old mice

• coronal sutures appear to already be fused and mineralized at E16.5

premature squamoparietal suture closure ( J:309253 )

• synostoses of the squamosal sutures are seen in 3-week-old mice

abnormal chondrocyte physiology ( J:309253 )

• E18.5 growth plate chondrocytes exhibit strong gammaH2AX staining indicating increased/unresolved DNA damage

increased chondrocyte apoptosis ( J:309253 )

• E18.5 growth plates show increased numbers of apoptotic cells

decreased chondrocyte proliferation ( J:309253 )

• E18.5 growth plates show reduced number of BrdU+ cells in the proliferating zone indicating decreased cell proliferation

cellular

increased chondrocyte apoptosis ( J:309253 )

• E18.5 growth plates show increased numbers of apoptotic cells

decreased chondrocyte proliferation ( J:309253 )

• E18.5 growth plates show reduced number of BrdU+ cells in the proliferating zone indicating decreased cell proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Baller-Gerold syndrome		DOID:0050654	OMIM:218600	J:309253
Rothmund-Thomson syndrome		DOID:2732	OMIM:268400	J:309253