Phenotypes associated with this allele

• Allele Symbol: Mmp14^tm1Hbh
• Allele Name: targeted mutation 1, Henning Birkedal-Hansen
• Allele ID: MGI:2445723
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mmp14^tm1Hbh/Mmp14^tm1Hbh	involves: 129P1/ReJ * 129P2/OlaHsd * Black Swiss	MGI:3583005
hm2	Mmp14^tm1Hbh/Mmp14^tm1Hbh	involves: 129P2/OlaHsd	MGI:3772054
hm3	Mmp14^tm1Hbh/Mmp14^tm1Hbh	involves: 129P2/OlaHsd * Black Swiss	MGI:3583010
cn4	Mmp14^tm1Hbh/Mmp14^tm1.1Khol Mmp15^tm1Kohl/Mmp15^tm1Kohl Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA	MGI:4868430
cx5	Mmp14^tm1Hbh/Mmp14^tm1Hbh Mmp16^tm1Khol/Mmp16^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3772052
cx6	Mmp14^tm1Hbh/Mmp14^tm1Hbh Mmp16^tm1Khol/Mmp16^tm1Khol	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3772048
cx7	Mmp14^tm1Hbh/Mmp14^+ Mmp16^tm1Khol/Mmp16^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3772056
cx8	Mmp14^tm1Hbh/Mmp14^tm1Hbh Mmp15^tm1Kohl/Mmp15^tm1Kohl	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:4868429
cx9	Mmp14^tm1Hbh/Mmp14^+ Mmp16^tm1Khol/Mmp16^tm1Khol	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3772055

Genotype
MGI:3583005

hm1

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh
• Genetic Background: involves: 129P1/ReJ * 129P2/OlaHsd * Black Swiss

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

respiratory system

impaired lung alveolus development ( J:97067 )

• demonstrated only a modest increase in alveolization from P1 to P14, however proximal lung branching was normal

abnormal club cell morphology ( J:97067 )

• Clara cells were flattened and lacked apical protrusions at the level of the terminal bronchiole

pulmonary hypoplasia ( J:97067 )

dilated pulmonary alveolar duct ( J:97067 )

• enlarged alveolar ducts

abnormal pulmonary alveolus morphology ( J:97067 )

• 40% less alveolar surface area and 46% greater alveolar diameter at 1 month of age with these differences persisting in adulthood and the surface area declining even more over time

overexpanded pulmonary alveolus ( J:97067 )

• 46% greater alveolar diameter at 1 month of age with difference persisting in adulthood

absent alveolar pores ( J:97067 )

• failed to develop pores of Kohn

abnormal pulmonary elastic fiber morphology ( J:97067 )

• showed slightly increased thickness of elastic fibers in alveolar walls

abnormal terminal bronchiole morphology ( J:97067 )

• Clara cells were flattened and lacked apical protrusions at the level of the terminal bronchiole

dilated respiratory conducting tube ( J:97067 )

• enlarged distal airways and the terminal airways extended to the pleural surface

Genotype
MGI:3772054

hm2

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh
• Genetic Background: involves: 129P2/OlaHsd

skeleton

decreased cranium length ( J:130212 )

• at day 20, the cranium length is reduced to 67+/-1.9% of wild-type

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 83+/-1.6% of wild-type

abnormal chondrocyte morphology ( J:130212 )

• the number of proliferating chondrocytes in the distal femoral epiphysis decreases proportionally to the number of wild-type alleles lost

limbs/digits/tail

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 83+/-1.6% of wild-type

craniofacial

decreased cranium length ( J:130212 )

• at day 20, the cranium length is reduced to 67+/-1.9% of wild-type

Genotype
MGI:3583010

hm3

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

mortality/aging

premature death ( J:57969 )

• most homozygotes that survived past weaning died between days 50 and 90 due to wasting

postnatal lethality, incomplete penetrance ( J:57969 )

• 33% died from wasting before weaning

reproductive system

absent sexual maturation ( J:57969 )

skeleton

abnormal cranium morphology ( J:57969 )

abnormal neurocranium morphology ( J:57969 )

• dysmorphic lower frontal regions of the calvarium due to delayed ossification of calvarial bones

abnormal fontanelle morphology ( J:57969 )

• larger fontanelles

abnormal interparietal bone morphology ( J:57969 )

• interparietal bone was displaced and ossification of the interparietal bone was incomplete by day 15 with the fibrous vestige of the cartilage primordium remaining rather than disappearing as in wild-type

abnormal parietal bone morphology ( J:57969 , J:86538 )

• only the outer bony plate forms in parietal bones, whereas the inner plate is replaced by remnants of the parietal cartilage anlage (J:86538)

abnormal orbit morphology ( J:57969 )

• gradually developed orbital protrusions that were obvious at day 5

domed cranium ( J:57969 )

• dome-shaped skill with bulging parietal and interparietal regions that was obvious at day 5

abnormal long bone morphology ( J:57969 )

• fibrosis, reduced cell proliferation and structural disorganization of the periosteal osteogenic layer of long bones was seen in 40 day or older homozygous null mice

decreased length of long bones ( J:57969 )

• limb bones appeared shorter and grew to approximately 65% of the length in controls by day 45

kyphosis ( J:57969 )

• progressively developed hyperkyphosis

lordosis ( J:57969 )

• progressively developed hyperlordosis

decreased bone mineral density ( J:57969 )

• became increasingly apparent as a result of increased bone resorption as well as diminished bone formation

abnormal trabecular bone morphology ( J:57969 )

• reduced trabecular bone in the spongiosa and a thinner cortex

osteoporosis ( J:57969 )

• severely reduced bone mass in 40 day or older homozygous null mice

abnormal cartilage morphology ( J:57969 )

abnormal Meckel's cartilage morphology ( J:86538 )

• complete proteoglycan depletion, numerous empty chondroctye lacunae, and apoptosis of residual chondrocytes are seen in Meckel's cartilage vestiges, indicating impaired remodeling of the posterior portion of Meckel's cartilage into bone and ligament

abnormal chondrocyte morphology ( J:57969 , J:86538 )

• reduced chondrocyte proliferation in growth plates of 39-day old, but not 10 day old, homozygous null mice (J:57969)

• empty chondrocyte lacunae are seen in cartilage vestiges (ghost cartilage) and remaining chondrocytes undergo apoptosis (J:86538)

• apoptotic calvarial chondrocytes are randomly distributed within the cartilage (J:86538)

abnormal joint morphology ( J:86538 )

• joints show ghost (empty lacunae) cartilages at sites of transition between different articular tissue

abnormal cranial suture morphology ( J:57969 )

• incomplete suture closure

abnormal skeleton development ( J:57969 , J:198679 )

• abnormal long bone development, with delayed ossification of the epiphysis and reduced longitudinal growth (J:57969)

• skeletal stem cells exhibit a stronger predisposition to commit to the adipocyte lineage compared with wild-type cells (J:198679)

• skeletal stem cells exhibit a heightened chondrogenic potential compared with wild-type cells (J:198679)

• transplanted skeletal stem cells exhibit impaired osteogenesis and enhanced adipogenic and chondrogenic potential compared with wild-type cell (J:198679)

impaired osteoblast differentiation ( J:198679 )

• in a 3D collagen hydrogels

abnormal long bone epiphyseal plate morphology ( J:57969 )

• metaphyseal growth plates showed progressive thinning, disorganization, and lack of chondrocyte proliferation

• delayed ossification of the epiphysis

abnormal cartilage development ( J:86538 )

• vestiges of embryonic cranial cartilages that precede membranous bone persist on the inner aspect of the skull up to 62 days of age

abnormal skeleton physiology ( J:57969 )

arthritis ( J:57969 )

• developed severe generalized arthritis, with all joints showing overgrowth of a hypercellular, vascularized synovial tissue and destruction of articular cartilage, resulting in ankylosis

abnormal bone ossification ( J:57969 )

• bone formation was drastically reduced and vascular canals that invade uncalcified epiphyseal cartilage did not form

• parietal cartilage was never removed and was gradually transformed into an increasingly fibrotic and acellular vestige on the inner aspect of the underdeveloped parietal/interparietal bone, however endochondral ossification of the cartilage precursor of the pars petrosa occurred normally

delayed bone ossification ( J:57969 )

• delayed membranous ossification of calvarial bones and delayed postnatal development of the epiphyseal (secondary) ossification centers

abnormal bone remodeling ( J:86538 )

• impaired remodeling of unmineralized cartilage into cortical bone resulting in the retention of unmineralized portions of articular cartilages that would normally undergo resorption during growth

abnormal osteoclast physiology ( J:57969 , J:86538 )

• excessive osteoclastic resorption in all bones of mice aged 40 days or older (J:57969)

• although 62 day old mutants exhibit osteoclastic resorption of the parietal bone outer bony plate, the cartilage vestige occupying the region of the missing inner bony plate remains undegraded (J:86538)

growth/size/body

short snout ( J:57969 )

• obvious at P5

decreased body size ( J:57969 )

decreased body weight ( J:57969 )

• weight ranged from 3.5-5 grams versus 12-16 grams for wild-type, and gained little weight over time

cachexia ( J:57969 )

• progressive wasting

disproportionate dwarf ( J:57969 )

behavior/neurological

decreased locomotor activity ( J:57969 )

• progressively showed reduced mobility

vision/eye

abnormal orbit morphology ( J:57969 )

• gradually developed orbital protrusions that were obvious at day 5

integument

focal hair loss ( J:57969 )

• patchy hair loss over time

skin fibrosis ( J:57969 )

• progressive fibrosis was also seen in the dermis, hair follicles, and osteogenic periosteum

cellular

impaired osteoblast differentiation ( J:198679 )

• in a 3D collagen hydrogels

craniofacial

abnormal cranium morphology ( J:57969 )

abnormal cranial suture morphology ( J:57969 )

• incomplete suture closure

abnormal Meckel's cartilage morphology ( J:86538 )

• complete proteoglycan depletion, numerous empty chondroctye lacunae, and apoptosis of residual chondrocytes are seen in Meckel's cartilage vestiges, indicating impaired remodeling of the posterior portion of Meckel's cartilage into bone and ligament

abnormal neurocranium morphology ( J:57969 )

• dysmorphic lower frontal regions of the calvarium due to delayed ossification of calvarial bones

abnormal fontanelle morphology ( J:57969 )

• larger fontanelles

abnormal interparietal bone morphology ( J:57969 )

• interparietal bone was displaced and ossification of the interparietal bone was incomplete by day 15 with the fibrous vestige of the cartilage primordium remaining rather than disappearing as in wild-type

abnormal parietal bone morphology ( J:57969 , J:86538 )

• only the outer bony plate forms in parietal bones, whereas the inner plate is replaced by remnants of the parietal cartilage anlage (J:86538)

abnormal orbit morphology ( J:57969 )

• gradually developed orbital protrusions that were obvious at day 5

domed cranium ( J:57969 )

• dome-shaped skill with bulging parietal and interparietal regions that was obvious at day 5

short snout ( J:57969 )

• obvious at P5

immune system

abnormal osteoclast physiology ( J:57969 , J:86538 )

• excessive osteoclastic resorption in all bones of mice aged 40 days or older (J:57969)

• although 62 day old mutants exhibit osteoclastic resorption of the parietal bone outer bony plate, the cartilage vestige occupying the region of the missing inner bony plate remains undegraded (J:86538)

arthritis ( J:57969 )

• developed severe generalized arthritis, with all joints showing overgrowth of a hypercellular, vascularized synovial tissue and destruction of articular cartilage, resulting in ankylosis

limbs/digits/tail

abnormal forelimb morphology ( J:57969 )

• exhibited kinking of the wrist

hematopoietic system

abnormal osteoclast physiology ( J:57969 , J:86538 )

• excessive osteoclastic resorption in all bones of mice aged 40 days or older (J:57969)

• although 62 day old mutants exhibit osteoclastic resorption of the parietal bone outer bony plate, the cartilage vestige occupying the region of the missing inner bony plate remains undegraded (J:86538)

muscle

skeletal muscle fibrosis ( J:57969 )

• tendons, ligaments, synovial capsules, musculotendinal junctions, and septal/fascial structures associated with skeletal muscle all displayed increased cell proliferation and vascularity and became increasingly fibrotic

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rheumatoid arthritis		DOID:7148	OMIM:180300	J:57969

Genotype
MGI:4868430

cn4

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1.1Khol; Mmp15^tm1Kohl/Mmp15^tm1Kohl; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA

embryo

abnormal placental labyrinth vasculature morphology ( J:167396 )

• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice

absent placental labyrinth ( J:167396 )

• at E12.5 in tamoxifen-treated mice starting at E7.5

• however, placenta develops normally in mice treated with tamoxifen at E12.5

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:167396 )

N • tamoxifen-treated mice exhibit normal mammary gland involution

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:167396 )

• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice

Genotype
MGI:3772052

cx5

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh; Mmp16^tm1Khol/Mmp16⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

postnatal lethality, complete penetrance ( J:130212 )

• mice have a median survival of 16 days after birth

skeleton

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

abnormal long bone morphology ( J:130212 )

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 76+/-4.82% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 74+/-3.3% of wild-type

• however, length at day 30 is normal

abnormal compact bone morphology ( J:130212 )

• cortical bone formation is abnormal and the humeri and femora exhibit shortening of the bone cortices proportional to the number of wild-type alleles lost

abnormal cartilage morphology ( J:130212 )

abnormal long bone epiphyseal plate proliferative zone ( J:130212 )

• the proliferating zone contains fewer cells than in wild-type mice but not as few as in Mmp14^tm1Hbh Mmp16^tm1Khol double homozygotes

abnormal long bone hypertrophic chondrocyte zone ( J:130212 )

• the hypertrophic chondrocyte zone is elongated compared to in wild-type mice but not as much as in Mmp14^tm1Hbh Mmp16^tm1Khol double homozygotes

abnormal chondrocyte morphology ( J:130212 )

• the number of proliferating chondrocytes in the distal femoral epiphysis decreases proportionally to the number of wild-type alleles lost

decreased bone ossification ( J:130212 )

• mice exhibit diminished bone formation

limbs/digits/tail

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 76+/-4.82% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 74+/-3.3% of wild-type

• however, length at day 30 is normal

craniofacial

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

respiratory system

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

growth/size/body

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

Genotype
MGI:3772048

cx6

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh; Mmp16^tm1Khol/Mmp16^tm1Khol
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

neonatal lethality, complete penetrance ( J:130212 )

• all but one mice die within 1 day of birth

skeleton

abnormal skeleton morphology ( J:130212 )

• apoptosis of skeletal cells is increased 280+/-70% compared to in wild-type mice

• the number of bone lining cells is decreased compared to in wild-type mice and the majority of connective tissue cells are dispersed between individual bone trabeculae

abnormal cranium morphology ( J:130212 )

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

abnormal parietal bone morphology ( J:130212 )

• the parietal bone near the sagittal suture is abnormal and contains azurophilic patches

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

pterygoid bone hypoplasia ( J:130212 )

• the pterygoid bone is underdeveloped

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

abnormal mandible morphology ( J:130212 )

• trabeculae of the mandible are aberrant and thin compared to in wild-type mice

maxilla hypoplasia ( J:130212 )

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

absent palatine bone ( J:130212 )

abnormal vomer bone morphology ( J:130212 )

• mice exhibit pitting and lack of fusion to the maxilla

vomer bone hypoplasia ( J:130212 )

• mice exhibit hypoplasia of the vomer

domed cranium ( J:130212 )

• mice exhibit a domed skull that is more severe than in Mmp14^tm1Hbh homozygotes

abnormal long bone morphology ( J:130212 )

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 51+/-4.75% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 65+/-2.5% of wild-type

• however, length at day 30 is normal

abnormal compact bone morphology ( J:130212 )

• cortical bone formation is abnormal and the humeri and femora exhibit shortening of the bone cortices proportional to the number of wild-type alleles lost

absent bone trabeculae ( J:130212 )

• mice exhibit a lack of trabeculae in the marrow cavity

abnormal cartilage morphology ( J:130212 )

abnormal Meckel's cartilage morphology ( J:130212 )

• Meckel's cartilage is conspicuous in size

abnormal long bone epiphyseal plate proliferative zone ( J:130212 )

• the proliferating zone contains fewer cells than in wild-type mice

abnormal long bone hypertrophic chondrocyte zone ( J:130212 )

• the hypertrophic chondrocyte zone is elongated compared to in wild-type mice

abnormal chondrocyte morphology ( J:130212 )

• the number of proliferating chondrocytes in the distal femoral epiphysis decreases proportionally to the number of wild-type alleles lost to 25.7+/-4.8% of wild-type

decreased bone ossification ( J:130212 )

• unlike in wild-type mice primary ossification centers are occupied by un-degraded hypertrophic cartilage

• mice exhibit diminished bone formation

growth/size/body

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

palatal shelves fail to meet at midline ( J:130212 )

• fusion is absent

palatal shelf hypoplasia ( J:130212 )

• palatial shelf growth is reduced

abnormal midface morphology ( J:130212 )

• mice exhibit a shorter mid-face than in Mmp14^tm1Hbh homozygotes

cleft secondary palate ( J:130212 )

• 80% of mice exhibit cleft palates

short snout ( J:130212 )

decreased body size ( J:130212 )

• mice are born small, moribund and fail to eat

limbs/digits/tail

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 51+/-4.75% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 65+/-2.5% of wild-type

• however, length at day 30 is normal

short limbs ( J:130212 )

craniofacial

abnormal cranium morphology ( J:130212 )

abnormal Meckel's cartilage morphology ( J:130212 )

• Meckel's cartilage is conspicuous in size

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

abnormal parietal bone morphology ( J:130212 )

• the parietal bone near the sagittal suture is abnormal and contains azurophilic patches

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

pterygoid bone hypoplasia ( J:130212 )

• the pterygoid bone is underdeveloped

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

abnormal mandible morphology ( J:130212 )

• trabeculae of the mandible are aberrant and thin compared to in wild-type mice

maxilla hypoplasia ( J:130212 )

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

absent palatine bone ( J:130212 )

abnormal vomer bone morphology ( J:130212 )

• mice exhibit pitting and lack of fusion to the maxilla

vomer bone hypoplasia ( J:130212 )

• mice exhibit hypoplasia of the vomer

domed cranium ( J:130212 )

• mice exhibit a domed skull that is more severe than in Mmp14^tm1Hbh homozygotes

palatal shelves fail to meet at midline ( J:130212 )

• fusion is absent

palatal shelf hypoplasia ( J:130212 )

• palatial shelf growth is reduced

abnormal midface morphology ( J:130212 )

• mice exhibit a shorter mid-face than in Mmp14^tm1Hbh homozygotes

cleft secondary palate ( J:130212 )

• 80% of mice exhibit cleft palates

short snout ( J:130212 )

digestive/alimentary system

palatal shelves fail to meet at midline ( J:130212 )

• fusion is absent

palatal shelf hypoplasia ( J:130212 )

• palatial shelf growth is reduced

cleft secondary palate ( J:130212 )

• 80% of mice exhibit cleft palates

respiratory system

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

Genotype
MGI:3772056

cx7

• Allelic Composition: Mmp14^tm1Hbh/Mmp14⁺; Mmp16^tm1Khol/Mmp16⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

skeleton

decreased cranium length ( J:130212 )

• at day 30, the cranium length is reduced to 91% of wild-type

short humerus ( J:130212 )

• at day 20, humerus length is 94+/-1.2% of wild-type

• at day 50, humerus length is 93+/-0.7% of wild-type

abnormal chondrocyte morphology ( J:130212 )

• the number of proliferating chondrocytes in the distal femoral epiphysis decreases proportionally to the number of wild-type alleles lost

limbs/digits/tail

short humerus ( J:130212 )

• at day 20, humerus length is 94+/-1.2% of wild-type

• at day 50, humerus length is 93+/-0.7% of wild-type

craniofacial

decreased cranium length ( J:130212 )

• at day 30, the cranium length is reduced to 91% of wild-type

Genotype
MGI:4868429

cx8

• Allelic Composition: Mmp14^tm1Hbh/Mmp14^tm1Hbh; Mmp15^tm1Kohl/Mmp15^tm1Kohl
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:167396 )

• mice die between E10.5 and E11.5

embryo

embryonic growth retardation ( J:167396 )

• at E10.5

decreased embryo size ( J:167396 )

• at E10.5

abnormal placenta labyrinth morphology ( J:167396 )

• establishment of the labyrinthin layer of embryonic and maternal vascular interchange is retarded compared to in wild-type mice

• trophoblasts are present mostly as compact undifferentiated chorionic trophoblasts and far fewer as syncytiotrophoblast compared to in wild-type mice

• at E10.5, mice exhibit disruption of the labyrinth architecture compared with wild-type mice

abnormal placental labyrinth vasculature morphology ( J:167396 )

• the number of fetal vessels extending from the allantoic mesenchyme through the chorionic trophoblasts and into the labyrinth and the degree of branching of fetal vessels are diminished compared to in wild-type mice

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:167396 )

• the number of fetal vessels extending from the allantoic mesenchyme through the chorionic trophoblasts and into the labyrinth and the degree of branching of fetal vessels are diminished compared to in wild-type mice

dilated vasculature ( J:167396 )

• at E10.5

enlarged pericardium ( J:167396 )

• at E10.5

growth/size/body

embryonic growth retardation ( J:167396 )

• at E10.5

decreased embryo size ( J:167396 )

• at E10.5

Genotype
MGI:3772055

cx9

• Allelic Composition: Mmp14^tm1Hbh/Mmp14⁺; Mmp16^tm1Khol/Mmp16^tm1Khol
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

postnatal lethality, incomplete penetrance ( J:130212 )

• only 80% of mice survive until weaning

skeleton

decreased cranium length ( J:130212 )

• at day 30, the cranium length is reduced to 86% of wild-type

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 87+/-0.7% of wild-type

• at day 20, humerus length is 90+/-0.7% of wild-type

• at day 50, humerus length is 87+/-1% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 86+/-1% of wild-type

• however, length at day 30 is normal

abnormal compact bone morphology ( J:130212 )

• cortical bone formation is abnormal and the humeri and femora exhibit shortening of the bone cortices proportional to the number of wild-type alleles lost

abnormal chondrocyte morphology ( J:130212 )

• the number of proliferating chondrocytes in the distal femoral epiphysis decreases proportionally to the number of wild-type alleles lost

decreased bone ossification ( J:130212 )

• mice exhibit diminished bone formation

limbs/digits/tail

short humerus ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, humerus cortical length is 87+/-0.7% of wild-type

• at day 20, humerus length is 90+/-0.7% of wild-type

• at day 50, humerus length is 87+/-1% of wild-type

short femur ( J:130212 )

• severity is proportional to the number of wild-type alleles lost

• at E18.5, femur length is 86+/-1% of wild-type

• however, length at day 30 is normal

craniofacial

decreased cranium length ( J:130212 )

• at day 30, the cranium length is reduced to 86% of wild-type

frontal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the frontal bones

parietal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the parietal bones

thin neurocranium ( J:130212 )

• mice exhibit a thinning of the cranial vault proportional to the loss of wild-type alleles

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

short snout ( J:130212 )

• at day 75 the snout is shorter than in Mmp16^tm1Khol homozygotes

growth/size/body

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones

short snout ( J:130212 )

• at day 75 the snout is shorter than in Mmp16^tm1Khol homozygotes

respiratory system

nasal bone hypoplasia ( J:130212 )

• mice exhibit poor development of the nasal bones