Analysis Tools
mortality/aging
|
• homozygotes most likely die at birth due to suffocation
|
growth/size/body
|
• fusion of the tongue to the developing palatal prevents secondary palate formation
|
|
• fusion between the palatal shelves and the tongue at E15.5
|
cleft palate
(
J:259661
)
|
• failure to elevate palatal shelves leading to cleft palate at E15.5
|
|
• at E18.5, homozygotes display fusion of the oral opening
(J:78593)
• although the mouth cavity is initially formed at E12.5, the epithelia lining the oral cavity fuse completely at E13.5
(J:259661)
|
|
• at E18.5, homozygotes display fusion of the nasal opening
|
embryo
|
• E-cadherin, an adhesion molecule that is normally absent from the apical side of wild-type peridermal cells, is frequently localized apically in K17-positive peridermal cells lining the oral cavity, esophagus and skin
• ectopic localization of E-cadherin on the apical membrane of the outer peridermal cell layers likely explains the intraoral and esophageal fusions and the partial attachment of the limbs to the body wall
|
|
• outermost epidermal cell layers are nucleated and have microvilli at the apical surface indicative of periderm cells while patches of anuclear corneocytes are found below the outermost nucleated cells
• presence of K6 and K17 confirms the peridermal nature of the outermost skin layers which persists to E18.5, whereas wild-type embryos are devoid of periderm at E18.5
• presence of nuclei in the most superficial layers of skin is likely due to impaired periderm shedding, rather than parakeratosis as initially suggested
• defect in periderm shedding at E18.5 could be due to incomplete cornification and lack of proteasomal degradation of desmosomes; intact desmosomes are detected within and between the cornified patches and periderm of skin at E18.5
• abnormal suprabasal and peridermal proliferation is seen in E16.5 skin, as determined by the presence of BrdU positivity, multiple p63-positive nuclei and peridermal marker K17 staining
|
craniofacial
|
• fusion of the tongue to the developing palatal prevents secondary palate formation
|
|
• fusion between the palatal shelves and the tongue at E15.5
|
cleft palate
(
J:259661
)
|
• failure to elevate palatal shelves leading to cleft palate at E15.5
|
|
• at E18.5, homozygotes display fusion of the oral opening
(J:78593)
• although the mouth cavity is initially formed at E12.5, the epithelia lining the oral cavity fuse completely at E13.5
(J:259661)
|
|
• at E18.5, homozygotes display fusion of the nasal opening
|
homeostasis/metabolism
|
• dye exclusion assays show that toluidine blue and lucifer yellow penetrate the skin at E18.5, indicating that a mature outside-in barrier is not formed
• at E18.5, the biotin tracer fails to stop at the transition of the upper granular layer to the cornified layer and diffuses to the top layers of the skin, indicating that a functional inside-out barrier is absent
• however, the biotin tracer is excluded from the cornified patches present in skin, suggesting that the barrier is functional at these patches
|
integument
|
• homozygotes display improper differentiation of epidermal keratinocytes, resulting in epidermal hyperplasia and absence of the stratum corneum
(J:78593)
• notably, mutant skin fails to fully differentiate when grafted onto a wild-type host; instead, abnormal hair follicle development and epidermal dysplasia indicative of progression into a more pathologic state are observed, suggeting a putative role in hair follicle growth and/or development
(J:78593)
• at E18.5, K14 staining is abnormally detected in the outermost cell layers of skin, indicating their undifferentiated status; a thick superficial layer of immature, K6-positive nucleated cells is present in skin while interspersed patches of differentiated keratinocytes are found internally
(J:259661)
• in vitro, primary keratinocytes fail to differentiate in the presence of Ca2+ or vitamin D, as shown by the lack of profilaggrin and caspase-14 expression
(J:259661)
|
|
• dye exclusion assays show that toluidine blue and lucifer yellow penetrate the skin at E18.5, indicating that a mature outside-in barrier is not formed
• at E18.5, the biotin tracer fails to stop at the transition of the upper granular layer to the cornified layer and diffuses to the top layers of the skin, indicating that a functional inside-out barrier is absent
• however, the biotin tracer is excluded from the cornified patches present in skin, suggesting that the barrier is functional at these patches
|
|
• at E17.5 and E18.5, mutant fetuses display poorly developed vibrissae
• however, no other obvious hair follicle defects are observed at E18.5
|
|
• at E18.5, homozygotes lack whiskers
|
|
• at E18.5, the outermost cornified layers are absent and replaced by severeal layers of nucleated parakeratotic cells
|
parakeratosis
(
J:78593
)
|
• at E18.5, the outermost cornified layers are replaced by a thick layer of flattened, parakeratotic cells
• some areas of orthokeratosis, appearing as a thin anuclear keratin layer below the parakeratotic layer, are also observed
• the outer most parakeratotic layer apperas to be largely undifferentiated and shows features of more basal cells, as revealed by expression analysis of keratins and differentiation markers
|
|
• at E18.5, homozygotes display increased thickness of the suprabasal layers of the skin, in the absence of increased proliferation
|
|
• at E18.5, mutant skin display significant hyperplasia of the granular and spinous layers
|
|
• at E18.5, mutant skin display a significant increase in the thickness of the spinous and granular layers
|
|
• at E17.5 and E18.5, mutant skin is significantly reduced in skin folds and has a smooth outer surface
|
thick skin
(
J:78593
)
|
• at E18.5, mutant skin is nearly 3 times thicker than wild-type skin
|
limbs/digits/tail
|
• at E18.5, mutant paws display fusion of the epithelium between digits
|
|
• at E17.5, the forelimbs are partially fused to lateral body surfaces
|
|
• at E17.5 and E18.5, mutant fetuses display shorter hindlimbs that are partially fused to the body cavity
(J:78593)
• at E17.5, the hindlimbs are partially fused to lateral body surfaces
(J:259661)
|
|
• short hindlimbs at E17.5 and E18.5
|
|
• at E17.5 and E18.5, mutant fetuses display shorter tails that are partially fused to the body cavity
|
short tail
(
J:78593
)
|
• short tails at E17.5 and E18.5
|
cellular
|
• at E18.5, epidermal cells show a strong reduction or absence of the membrane-associated F-actin network that is enriched at cell-cell contacts
|
|
• homozygotes display improper differentiation of epidermal keratinocytes, resulting in epidermal hyperplasia and absence of the stratum corneum
(J:78593)
• notably, mutant skin fails to fully differentiate when grafted onto a wild-type host; instead, abnormal hair follicle development and epidermal dysplasia indicative of progression into a more pathologic state are observed, suggeting a putative role in hair follicle growth and/or development
(J:78593)
• at E18.5, K14 staining is abnormally detected in the outermost cell layers of skin, indicating their undifferentiated status; a thick superficial layer of immature, K6-positive nucleated cells is present in skin while interspersed patches of differentiated keratinocytes are found internally
(J:259661)
• in vitro, primary keratinocytes fail to differentiate in the presence of Ca2+ or vitamin D, as shown by the lack of profilaggrin and caspase-14 expression
(J:259661)
|
digestive/alimentary system
|
• fusion of the tongue to the developing palatal prevents secondary palate formation
|
|
• fusion between the palatal shelves and the tongue at E15.5
|
cleft palate
(
J:259661
)
|
• failure to elevate palatal shelves leading to cleft palate at E15.5
|
anal atresia
(
J:78593
)
|
• at E18.5, homozygotes display fusion of the anal opening
|
|
• at E18.5, homozygotes display absence of the esophageal lumen
(J:78593)
• this atresia continues through the esophagus into the squamous part of the stomach
(J:78593)
• at E14.5, the esophageal lumen is fused
(J:259661)
|
reproductive system
|
• at E17.5, the genital tubercle and urogenital groove are absent
|
respiratory system
|
• at E18.5, homozygotes display fusion of the nasal opening
|
hematopoietic system
| N |
• no defects are observed within the B cell compartment in homozygous mutant radiation chimeras, as determined by flow cytometry and germinal-center formation
|
immune system
| N |
• no defects are observed within the B cell compartment in homozygous mutant radiation chimeras, as determined by flow cytometry and germinal-center formation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| popliteal pterygium syndrome | DOID:0060055 |
OMIM:119500 OMIM:263650 |
J:183160 , J:191507 | |
