Mouse Genome Informatics
ht
    Col1a1Aga2/Col1a1+
involves: C3HeB/FeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Col1a1Aga2/Col1a+ mice display skeletal and growth abnormalities

mortality/aging
• large subset of heterozygotes die postnatally

growth/size
• animals are smaller than wild-type littermates; at 9 weeks, all animals examined have 'slender' bodies relative to controls
• at 16 weeks, average body mass is ~20 grams compared to wild-type body mass of ~32 grams
• at 16 weeks, average body length is ~8.9 cm compared to ~10 cm in wild-type

nervous system
• intracranial hemorrhages are seen in subset of heterozygotes that die postnatally

skeleton
• skeletal phenotype is detectable between 6 and 11 days after birth
• animals reaching adulthood display mildly to moderately dystrophic limbs
• subset of heterozygotes that die postnatally show thin calvaria
• femoral periosteum at 12 weeks displays greater caspase 3-immunoreactivity indicating an elevated basal level of apoptosis (~14% higher relative to controls); an increased number of TUNEL-positive cells is observed in periosteum also
• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type
• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type
• ~50% of animals have deformed fibulae at 16 weeks of age
• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated ischium
• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated pubis region
• at 16 weeks, all animals examined show kyphoscoliosis
• at 16 weeks, bone mineral content is ~309 mg compared to ~935 mg in wild-type animals
• at 16 weeks, bone mineral density (without head) is 42 mg/cm2 compared to ~58 mg/cm2 in wild-type
• cortical structure has less-parallel, less-densely packed network of collagen bundles compared to controls
• cultured primary calvarial osteoblasts (OBs) show growth anomalies, with stimulated OBs displaying a limited saturation density
• formation of bone-like nodules by cultured calvarial osteoblasts (OBs) is reduced between 9 and 16 days in culture compared to wild-type cells; average area of individual nodules is reduced relative to controls
• nodular Alizarin red-binding capacity (staining for calcium in bone) is reduced 3.2 fold, indicative of decreased calcium deposition by osteoblasts
• after induction of cytoprotective unfolded protein response in cultured calvarial OBs, apoptosis is elevated compared to controls, with a 10% relative increase in TUNEL-positive picnotic OBs at 16 days in culture
• at 16 weeks, significant numbers of heterozygotes show a variety of bone fractures, including the tibia, humerus, ulna, and radius whereas no fractures are observed in wild-type

limbs/digits/tail
• femoral periosteum at 12 weeks displays greater caspase 3-immunoreactivity indicating an elevated basal level of apoptosis (~14% higher relative to controls); an increased number of TUNEL-positive cells is observed in periosteum also
• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type
• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type
• ~50% of animals have deformed fibulae at 16 weeks of age

craniofacial
• subset of heterozygotes that die postnatally show thin calvaria

homeostasis/metabolism
• total alkaline phosphatase levels are significantly elevated compared to wild-type littermates at 16 weeks
• mice have elevated calcitonin levels (pg/ml), compared to controls; elevation is more pronounced in female heterozygotes
• mice have elevated parathyroid hormone (PTH) levels (pg/ml), compared to wild-type littermates

reproductive system
• female heterozygotes produce smaller litters as result of reduced body size

cardiovascular system
• subset of heterozygotes that die postnatally show hemorrhaging at joint cavities
• intracranial hemorrhages are seen in subset of heterozygotes that die postnatally

adipose tissue
• at 16 weeks, subcutaneous fat span is ~2.9 mm compared to ~5.1 mm in wild-type

integument
• dermis contains more heterogeneous populations of fibroblasts with smaller nuclei, aberrant dilated electron-dense endoplasmic reticula (ERs), lysosomes, and empty autophagic-like vacuoles interspersed throughout the cells

Mouse Models of Human Disease
OMIM IDRef(s)
Osteogenesis Imperfecta, Type II 166210 J:129569