Phenotypes associated with this allele

• Allele Symbol: Col1a1^Aga2
• Allele Name: abnormal gait 2
• Allele ID: MGI:3769585
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Col1a1^Aga2/Col1a1^Aga2	involves: C3HeB/FeJ * C57BL/6J	MGI:3769906
ht2	Col1a1^Aga2/Col1a1^+	C3HeB/FeJ-Col1a1^Aga2	MGI:5431996
ht3	Col1a1^Aga2/Col1a1^+	involves: C3HeB/FeJ * C57BL/6J	MGI:3769907

Genotype
MGI:3769906

hm1

• Allelic Composition: Col1a1^Aga2/Col1a1^Aga2
• Genetic Background: involves: C3HeB/FeJ * C57BL/6J

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

mortality/aging

embryonic lethality, complete penetrance ( J:129569 )

• homozygous embryos display gestational arrest at ~9.5 dpc (days post coitum)

Genotype
MGI:5431996

ht2

• Allelic Composition: Col1a1^Aga2/Col1a1⁺
• Genetic Background: C3HeB/FeJ-Col1a1^Aga2

mortality/aging

postnatal lethality, incomplete penetrance ( J:185988 )

• mice with a severe phenotype display postnatal lethality

• lethality is not rescued by bisphosphonate alendronate treatment

• mice with a mild phenotype survive to adulthood

cardiovascular system

abnormal blood vessel morphology ( J:185988 )

• in mice with a severe phenotype cardiac vessels have disordered cell arrangements and thinner walls

abnormal myocardium layer morphology ( J:185988 )

• mice with a severe phenotype display reduction in the amount of collagen and a disordered collagen matrix with fewer and thinner collagen fibrils

heart right ventricle hypertrophy ( J:185988 )

• in mice with a severe phenotype

abnormal heart septum morphology ( J:185988 )

• enlarged septa in mice with a severe phenotype

abnormal cardiovascular system physiology ( J:185988 )

• mice with a severe phenotype display a septal deformation with a convex bulge into the left ventricle during contraction

pulmonary alveolar hemorrhage ( J:185988 )

• in mice with a severe phenotype

decreased heart left ventricle muscle contractility ( J:185988 )

• left ventricular end-systolic internal diameter is increased resulting in a reduced ejection fraction in mice with a severe phenotype

abnormal heart electrocardiography waveform feature ( J:185988 )

• extended J-T interval in mice with a mild phenotype

increased QRS amplitude ( J:185988 )

• in mice with a mild phenotype

respiratory system

pulmonary alveolar hemorrhage ( J:185988 )

• in mice with a severe phenotype

lung inflammation ( J:185988 )

• infiltrates of polymorphonuclear neutrophils and alveolar macrophages in mice with a severe phenotype

cellular

abnormal cell morphology ( J:185988 )

• cardiac fibroblasts from mice with a severe phenotype show disordered cytoplasm and Golgi abnormalities

• cardiac fibroblasts from mice with a severe or mild phenotype show a strong or slight decrease in collagen staining, respectively

• marginal decrease in collagen in lung fibroblasts from mice with a severe phenotype

abnormal Golgi apparatus morphology ( J:185988 )

• in cardiac fibroblasts

abnormal endoplasmic reticulum morphology ( J:185988 )

• in cardiac fibroblasts from mice with a severe phenotype

growth/size/body

heart right ventricle hypertrophy ( J:185988 )

• in mice with a severe phenotype

decreased body weight ( J:185988 )

• at 6-11 days of age in mice with a mild phenotype weight is 75% that of wild-type mice

• at 6-11 days of age in mice with a severe phenotype weight is 53% that of wild-type mice

skeleton

rib fractures ( J:185988 )

• rib fractures with callus formation are equally frequent in mice with severe or mild phenotypes

homeostasis/metabolism

abnormal blood gas level ( J:185988 )

• reduction of 44% in arterial pO2 and an increase of 40% in pCO2 accompanied by a 61% decrease in oxygen saturation in mice with a severe phenotype

immune system

lung inflammation ( J:185988 )

• infiltrates of polymorphonuclear neutrophils and alveolar macrophages in mice with a severe phenotype

muscle

abnormal myocardium layer morphology ( J:185988 )

• mice with a severe phenotype display reduction in the amount of collagen and a disordered collagen matrix with fewer and thinner collagen fibrils

heart right ventricle hypertrophy ( J:185988 )

• in mice with a severe phenotype

decreased heart left ventricle muscle contractility ( J:185988 )

• left ventricular end-systolic internal diameter is increased resulting in a reduced ejection fraction in mice with a severe phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta type 3		DOID:0110339	OMIM:259420	J:185988

Genotype
MGI:3769907

ht3

• Allelic Composition: Col1a1^Aga2/Col1a1⁺
• Genetic Background: involves: C3HeB/FeJ * C57BL/6J

Col1a1^Aga2/Col1a⁺ mice display skeletal and growth abnormalities

mortality/aging

postnatal lethality, incomplete penetrance ( J:129569 )

• large subset of heterozygotes die postnatally

cellular

abnormal osteoblast physiology ( J:129569 )

• 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

increased osteoblast apoptosis ( J:129569 )

• 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

growth/size/body

decreased body size ( J:129569 )

• animals are smaller than wild-type littermates; at 9 weeks, all animals examined have 'slender' bodies relative to controls

decreased body weight ( J:129569 )

• at 16 weeks, average body mass is ~20 grams compared to wild-type body mass of ~32 grams

decreased body length ( J:129569 )

• at 16 weeks, average body length is ~8.9 cm compared to ~10 cm in wild-type

nervous system

intracranial hemorrhage ( J:129569 )

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

skeleton

abnormal osteoblast physiology ( J:129569 )

• 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

increased osteoblast apoptosis ( J:129569 )

• 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

abnormal skeleton morphology ( J:129569 )

• skeletal phenotype is detectable between 6 and 11 days after birth

• animals reaching adulthood display mildly to moderately dystrophic limbs

thin neurocranium ( J:129569 )

• subset of heterozygotes that die postnatally show thin calvaria

abnormal femur morphology ( J:129569 )

• 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

decreased diameter of femur ( J:129569 )

• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type

short femur ( J:129569 )

• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type

abnormal fibula morphology ( J:129569 )

• ~50% of animals have deformed fibulae at 16 weeks of age

abnormal ischium morphology ( J:129569 )

• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated ischium

abnormal pubis morphology ( J:129569 )

• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated pubis region

kyphoscoliosis ( J:129569 )

• at 16 weeks, all animals examined show kyphoscoliosis

decreased bone mineral content ( J:129569 )

• at 16 weeks, bone mineral content is ~309 mg compared to ~935 mg in wild-type animals

decreased bone mineral density ( J:129569 )

• at 16 weeks, bone mineral density (without head) is 42 mg/cm² compared to ~58 mg/cm² in wild-type

abnormal compact bone lamellar structure ( J:129569 )

• cortical structure has less-parallel, less-densely packed network of collagen bundles compared to controls

abnormal osteoblast morphology ( J:129569 )

• cultured primary calvarial osteoblasts (OBs) show growth anomalies, with stimulated OBs displaying a limited saturation density

fragile skeleton ( J:129569 )

• 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

abnormal femur morphology ( J:129569 )

• 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

decreased diameter of femur ( J:129569 )

• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type

short femur ( J:129569 )

• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type

abnormal fibula morphology ( J:129569 )

• ~50% of animals have deformed fibulae at 16 weeks of age

craniofacial

thin neurocranium ( J:129569 )

• subset of heterozygotes that die postnatally show thin calvaria

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:129569 )

• total alkaline phosphatase levels are significantly elevated compared to wild-type littermates at 16 weeks

decreased circulating alkaline phosphatase level ( J:129569 )

abnormal hormone level ( J:129569 )

• mice have elevated calcitonin levels (pg/ml), compared to controls; elevation is more pronounced in female heterozygotes

increased circulating parathyroid hormone level ( J:129569 )

• mice have elevated parathyroid hormone (PTH) levels (pg/ml), compared to wild-type littermates

reproductive system

decreased litter size ( J:129569 )

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

cardiovascular system

hemorrhage ( J:129569 )

• subset of heterozygotes that die postnatally show hemorrhaging at joint cavities

intracranial hemorrhage ( J:129569 )

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

adipose tissue

abnormal adipose tissue distribution ( J:129569 )

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

integument

abnormal dermal layer morphology ( J:129569 )

• 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		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta type 2		DOID:0110341	OMIM:166210	J:129569