Mouse Genome Informatics
hm1
    Fgfr3tm1.1Iwa/Fgfr3tm1.1Iwa
involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes are never observed after birth


Mouse Genome Informatics
hm2
    Fgfr3tm1.1Iwa/Fgfr3tm1.1Iwa
involves: 129S6/SvEvTac * NIH Black Swiss * CD-1 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no homozygotes are found after birth, indicating lethality during gestation


Mouse Genome Informatics
ht3
    Fgfr3tm1.1Iwa/Fgfr3+
involves: 129S6/SvEvTac * Black Swiss * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some of the remaining mutants (about 25%) live beyond 3 months of age
• Background Sensitivity: backcrossing further to wild-type mice results in a greater frequency of severely affected mice with >10% of animals surviving beyond 3 months
• a subset of animals (around 50%) die before 4 weeks of age, by passing the perinatal lethality observed in Fgfr3 mutants

growth/size
• animals in the group that die before 4 weeks have significantly smaller size relative to wild-type littermates; surviving, mildly affected mice are smaller than wild-type littermates with body size intermediate between severely affected and wild-type animals

limbs/digits/tail
• limbs are shorter than wild-type littermates

craniofacial
• at P1 mutants can be identified by a mildly rounded head
• most of the severely affected animals exhibit malocclusion, whereas mildly affected animals do not

skeleton
• at P1 mutants can be identified by a mildly rounded head
• most of the severely affected animals exhibit malocclusion, whereas mildly affected animals do not
• at P4, rib cage of mutants is noticeably smaller than wild-type
• mice exhibit curvature of the axial skeleton
• at 15 months, marked thickening and the clonal proliferation of chondrocytes is observed
• postnatal growth plate chondrocytes show decreased proliferation compared to wild-type
• proliferating chondrocytes are scattered in proliferating and resting zones of growth plates
• ingrowth of mesenchymal tissue across the physis in P17 growth plates
• mutant costal cartilage displays a thinner layer of perichondrium compared to wild-type
• costal cartilage is thickened at P1
• proliferating chondrocytes are observed in proliferating and resting zones of long bone growth plates and throughout costal cartilage
• proliferation indices of growth plate chondrocytes are increased at E15.5 and E18.5 compared to wild-type
• overgrowth of hyaline cartilage including the trachea and the nasal septa is observed
• limbs have a shortened ossified zone
• delayed sternabrae ossification is observed at P1
• formation of the secondary ossification center is delayed

reproductive system
• some mutant animals surviving to adulthood are fertile


Mouse Genome Informatics
ht4
    Fgfr3tm1.1Iwa/Fgfr3+
involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• one set of mutants (52%) that are very small, die 4 weeks after birth
• 24% of mildly affected mutants live longer than 3 months, including some up to as long as wild-type
• Background Sensitivity: on a CD background, about 46% that are severely affected die early while 14% live longer than 3 months

growth/size
• those that die 4 weeks after birth are very small

craniofacial
• enlarged hyoid bone
• seen in severely affected mice, although some several severely affected mice die without malocclusion
• distinguishable at birth by a mildly round head

limbs/digits/tail
• shorter limbs with particularly shortened ossified zone

skeleton
• enlarged hyoid bone
• seen in severely affected mice, although some several severely affected mice die without malocclusion
• wider and shorter limb long bones
• delay in sternabrae ossification at P1
• thickening and slight bifurcation of the costal cartilage is seen at P1 and at 15 months of age
• at 15 months of age, observe clonal proliferation of chondrocytes in costal cartilage
• thinner layer of perichondrium in costal cartilage
• smaller rib cage is evident after P4
• exhibit curvature of the axial skeleton
• decrease in chondrocyte differentiation
• exhibit abnormal chondrocyte proliferation, with increased proliferation during embryo development but decreased proliferation in the postnatal growth plate chondrocytes
• chondrocytes in the medial part of the femur are smaller and premature at E15.5
• chondrocytes around the blood vessel in epiphysis are smaller at P4
• overgrowth of hyaline cartilage, including the trachea and the nasal septa and hypertrophy of the thyroid, cricoid, and tracheal cartilages
• growth plates at the junctions of the rib-bone and the costal cartilage at P17 are abnormal
• exhibit ingrowth of mesenchymal tissue across the physis at P17
• some undifferentiated chondrocytes intermingle with the hypertrophic chondrocytes at E15.5
• thicker growth plate with shorter hypertrophic zones and proliferating columns at P17
• chondrocytes have shorter columnar structures of the proliferating zone
• hypertrophic chondrocytes are sparse and not fully mature
• delay formation of the secondary ossification center
• delay in sternabrae ossification at P1

Mouse Models of Human Disease
OMIM IDRef(s)
Achondroplasia; ACH 100800 J:70061