Phenotypes associated with this allele

• Allele Symbol: Mia3^tm1Lex
• Allele Name: targeted mutation 1, Lexicon Pharmaceuticals
• Allele ID: MGI:5007248
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mia3^tm1Lex/Mia3^tm1Lex	involves: 129S5/SvEvBrd * C57BL/6	MGI:5009425

Genotype
MGI:5009425

hm1

• Allelic Composition: Mia3^tm1Lex/Mia3^tm1Lex
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

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

Mia3^tm1Lex/Mia3^tm1Lex embryos are dwarfed, edemic, and fail to form a mineralized skeleton

mortality/aging

perinatal lethality, complete penetrance ( J:172737 )

• all die at birth

respiratory system

respiratory failure ( J:172737 )

• neonates fail to breathe

growth/size/body

short snout ( J:172737 )

• at E15.5 - E16.5

disproportionate dwarf ( J:172737 )

• short limbed dwarfism

decreased fetal size ( J:172737 )

• subtle reduction in stature at E15.5 - E16.5

• body axis is shortened by about 50% compared to controls at E18.5

skeleton

decreased osteoblast cell number ( J:172737 )

• severe reduction on osteopontin-positive osteoblasts at E14.5

• at E14.5 the few osteoblasts detected are primarily in the periphery of the perichondrium adjacent to the hypertrophic region at the middle of the condensation

• at E16.5 more osteoblasts are present within the center of each bone although numbers are still reduced compared to controls and cells are restricted to an area immediately underlying the perichondrium

absent bone trabeculae ( J:172737 )

• complete absence of well define trabeculae at the diaphysis of the humeri

abnormal chondrocyte morphology ( J:172737 )

• marked distension of the ER in developing chondrocytes

• intracellular collagen aggregates

abnormal skeleton development ( J:172737 )

• severe defects in vascular invasion and recruitment of osteoblasts

abnormal cartilage development ( J:172737 )

• delay and arrest in chondrogenic maturation with profound defects in differentiation

delayed bone mineralization ( J:172737 )

• a delay in the onset of mineralization is seen at E13.5

• almost a complete lack of calcium deposits at E15.5

delayed bone ossification ( J:172737 )

• mineral deposition is seen at E18.5 but ossification is not detected

abnormal chondrocyte physiology ( J:172737 )

• at E13.5 maturing chondrocytes secrete very little collagen

• very little collagen is produced in chondrocyte enriched primary cell cultures and what is produced appears to be abnormally aggregated and unevenly dispersed throughout the extracellular fibrils

• at E14.5 Col2a1 is expressed and accumulates intracellularly but very little is detected extracellularly suggesting a defect in collagen secretion

• expression analysis indicates induction of the unfolded protein response in the cartilage from E14.5 to E16.5

cellular

abnormal cell morphology ( J:172737 )

• intracellular collagen aggregates are seen in multiple tissues, including the bone, skin, vasculature, smooth muscle, and skeletal muscle

abnormal cell physiology ( J:172737 )

• expression analysis indicates induction of the unfolded protein response in developing limbs

• impaired callagen secretion

cardiovascular system

internal hemorrhage ( J:172737 )

• subdermal microhemorrhages

homeostasis/metabolism

edema ( J:172737 )

• neonates are edemic

integument

abnormal cutaneous collagen fibril morphology ( J:172737 )

• intracellular collagen aggregates are seen in contrast to the fibrillar distribution seen in controls

abnormal dermal layer morphology ( J:172737 )

• at E15.5 - E16.5 the dermis appears tighter and less wrinkled than normal

decreased skin tensile strength ( J:172737 )

• skin and other tissues appear fragile during dissection

craniofacial

short snout ( J:172737 )

• at E15.5 - E16.5

limbs/digits/tail

short limbs ( J:172737 )

• at E15.5 - E16.5