mortality/aging
• less than 1% of mice survive to maturity
|
• almost all mice die within one day of birth
|
embryo
• at the 6 somite stage, the ectoderm in the primitive streak is often 1 or 2 cells thicker apically to basally and is more acutely folded
|
• at the 6 to 9 somite stage expression analysis indicates the posterior endoderm does not extend as far posteriorly and is delayed in folding ventrally to form the hindgut diverticulum
• at the 6 somite stage, the endoderm in the primitive streak is open ventrally failing to form a tubular hindgut
• by E10 absence of the tail gut is seen
|
sirenomelia
(
J:152701
)
• rare
|
• variable degrees of segmental truncation typically confined to the tail but sometimes involving the sacral or lumbar regions
|
• at E8.25 embryos are misshapen posterior to the somites in the region of the primitive streak
• at E8.25 the posterior region appears slightly spade shaped rather than rounded as in controls when viewed dorsally
• at the 6 to 7 somite stage the posterior length to width ratio is significantly decreased compared to controls
• however, the whole embryo length to width ratio is not significantly different from controls
|
• at the 6 to 9 somite stage expression analysis indicates the posterior endoderm does not extend as far posteriorly and is delayed in folding ventrally to form the hindgut diverticulum
|
• at E9.5, structures that normally separate left from right presomitic mesoderm terminate more anteriorly giving the tissue an abnormal Y shape rather than the normal U shape
|
• the volume of presomitic mesoderm is normal but it is redistributed around the shortened axial and ventral structures
• at E9.5, structures that normally separate left from right presomitic mesoderm terminate more anteriorly giving the tissue an abnormal Y shape rather than the normal U shape
|
spina bifida
(
J:152701
)
• seen in most mice with severe truncations
|
• by E10 the notochord is dramatically shorter compared to controls
|
• at the 6 somite stage all 3 germ layers are present but morphologically abnormal
|
• abnormalities are seen in somites formed at E9.5 or later
|
• expression analysis detects disruptions in somitogenesis after E10 that are always accompanied by anatomical abnormalities
|
• by E10 tail buds invariably show anatomical disorganization and evidence of histolysis
|
digestive/alimentary system
absent anus
(
J:152701
)
• by E10 absence of the tail gut is seen
|
• most neonates have blind-ended colons
|
• adults display megacolon probably resulting from impaired digestive tract evacuation
|
reproductive system
• seen in rare survivors
|
renal/urinary system
• invariably seen when kidneys are present
|
• in some mice
|
• midline fusion is seen in some mice
|
• ureters are present but most are connected at the midline or fused with the reproductive ducts
|
• lack a urinary outlet
|
• most neonates have no bladder
|
limbs/digits/tail
sirenomelia
(
J:152701
)
• rare
|
• by E10 tail buds invariably show anatomical disorganization and evidence of histolysis
|
• 73% display segmental truncation confined to the tail
|
short tail
(
J:152701
)
skeleton
• in 17% of mice segmental truncations extend into the sacral and lumbar regions
• typically the vertebrae immediately anterior to the truncation are smaller and malformed
|
• 73% display segmental truncation confined to the tail
|
nervous system
spina bifida
(
J:152701
)
• seen in most mice with severe truncations
|
cardiovascular system
• by E10 pockets of pooled blood and serous fluid are seen
|