mortality/aging
• mutants die soon after birth due to an inability to breathe
(J:57677)
• mice die at birth
(J:105944)
|
reproductive system
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• ovaries contain fewer germ cells that are found in clusters scattered throughout the ovary unlike in wild-type mice
|
• after 8 weeks of engraftment into a wild-type host, ovaries display oocyte degeneration or loss
|
• between E10.5 and E11.5, fewer than normal primordial germ cells migrate out of the hindgut resulting in fewer germ cells entering the developing gonads
• however, germ cell attractants are normally expressed
|
• ovaries lack distinct cortex and medulla regions as in wild-type ovaries
• granulosa and thecal cell layers as well as the basement membrane separating the two are less well defined than in wild-type mice
• after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice
• by week 8 after engraftment into a wild-type host, 1 of 4 ovaries contain Seroli cells tubule-like structures
|
• at E18.5, mutant ovaries lack a distinct cortex region
|
• by 8 weeks of engraftment into a wild-type host, remaining healthy follicles are larger than in wild-type mice
|
• when ovaries are transplanted into a wild-type host, follicles fail to progress beyond the pre-antral/early antral stages
|
• after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice
|
• at E18.5, mutant ovaries lack a distinct medulla region
|
small ovary
(
J:105944
)
• at E18.5, mutant ovaries are smaller than wild-type
|
ovary cyst
(
J:105944
)
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• seminiferous cords are present but interspersed with regions of disorganized cells where no cords are apparent
|
• at E18.5, testes exhibit a reduced tunica albuginea
|
• the oviduct is shorter than normal and uncoiled
|
small gonad
(
J:105944
)
• by E14.5, gonads are reduced compared to in wild-type mice
• mice exhibit smaller and misshapen gonads, especially in the posterior regions, compared to in wild-type mice
|
small testis
(
J:105944
)
|
embryo
• major malformations in the branchial arch arteries and heart are found in all double heterozygotes
|
• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4
|
• mice exhibit a reduction in the posterior mesonephros with abnormal indentation
• at E14.5, the mesonephric tissues remain enlarged compared to in wild-type mice
• ectopic mesonephric tubules persist up to E18.5
|
skeleton
• newborns have extinsive abnormalities in the skull, vertebrae, thorax, hyoid, larynx, and appendicular skeleton
|
• in newborns the basisphenoid bone is reduced and malformed
|
• in newborns the calvarial bones are absent
|
• the zygomatic process is enlarged and fused to the mandible
|
• in newborns the digits are thinner than normal with smaller ossification centers
|
• in newborns the deltoid process of the humerus is misshapen
|
• in newborns the xiphoid process is misshapen
|
• the absence of the sternum presumably contributes to the inability of these mutants to breath
|
• in newborns the dorsal neural arches fail to fuse along the whole vetebral column
• in newborns the lateral arches are reduced
• at E16.5 and birth the neural arches are misshapen and have reduced ossification
|
• in newborns the vetebral bodies are reduced
|
• ossification of some of bones is impaired
|
• in newborns all of the ossification centers of the sternum except the manubrium are absent
• at E13.5 the mesenchyme cells condense much less than in wild-type
|
vision/eye
• at E18.5, lactimal ducts are distended; the overall length of the gland duct is significantly reduced
|
• at E18.5, the exorbital lobe is severely reduced compared to in wild-type mice
• significantly fewer branches and terminal buds are observed within the exorbital lobe
|
• at E18.5, the intra-orbital lacrimal gland is absent
|
• at E16.5, branches of the lacrimal gland are shorter and wider with fewer terminal buds than in wild-type mice
• lacrimal gland explants have fewer branches with terminal buds that are longer and wider than in wild-type lacrimal explants
• however, lacrimal gland epithelium differentiation is normal
|
• lacrimal gland mesenchyme is insensitive to Bmp7 treatment unlike wild-type mesenchyme
• however, lacrimal gland epithelium proliferation in response to FGF is normal
|
• reduced number of mesenchymal cells in the future stromal region
|
• the arrangement of cells within the cornea is disorganized
|
• fails to differentiate normally
|
• cells become enlarged and separated from one another by microvilli lined spaces
|
• comes to be composed of more cell layers than normal
|
small lens
(
J:56425
)
• significantly reduced in size
|
• the eyelids are not fused at birth
|
• at E18.5, the lacrimal ducts are distended with individual buds shorter and wider than in wild-type mice
• the length of the ducts and number of terminal buds are reduced compared to in wild-type mice
|
cardiovascular system
• major malformations in the branchial arch arteries and heart are found in all double heterozygotes
|
• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4
|
• coarctation of the arch of the aorta is found at E11.5 and in newborns (3 out of 5 and 6 out of 11, respectively)
|
• at E13.5 and 16.5 interruption of the arch of the aorta is found (2 out of 3 and 2 out of 6 respectively)
|
• the ductus arteriosus connecting the aorta to the pulmonary artery fails to close in all newborns
|
• ventricular septal defects are found at E13.5, E16.5 and in newborns (2 out of 6; 2 out of 3; 8 out of 11, respectively)
|
• dysplasia
|
• in newborns the normal number of leaflets is found but these are thickened and partially fused (8 out of 11)
|
• dysplasia
|
• in newborns the normal number of leaflets is found but these are thickened and partially fused (8 out of 11)
|
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular
|
craniofacial
• major malformations in the branchial arch arteries and heart are found in all double heterozygotes
|
• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4
|
• in newborns the basisphenoid bone is reduced and malformed
|
• in newborns the calvarial bones are absent
|
• the zygomatic process is enlarged and fused to the mandible
|
homeostasis/metabolism
• 30% of embryos collected between E17.5 and E18.5 are dead or edematous (5 out of 15)
|
limbs/digits/tail
• in newborns the digits are thinner than normal with smaller ossification centers
|
• in newborns the deltoid process of the humerus is misshapen
|
nervous system
• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular
|
hydrocephaly
(
J:48079
)
• by E11.5 the brain size is clearly increased in mutants
• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular
|
endocrine/exocrine glands
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• at E18.5, lactimal ducts are distended; the overall length of the gland duct is significantly reduced
|
• at E18.5, the exorbital lobe is severely reduced compared to in wild-type mice
• significantly fewer branches and terminal buds are observed within the exorbital lobe
|
• at E18.5, the intra-orbital lacrimal gland is absent
|
• at E16.5, branches of the lacrimal gland are shorter and wider with fewer terminal buds than in wild-type mice
• lacrimal gland explants have fewer branches with terminal buds that are longer and wider than in wild-type lacrimal explants
• however, lacrimal gland epithelium differentiation is normal
|
• ovaries lack distinct cortex and medulla regions as in wild-type ovaries
• granulosa and thecal cell layers as well as the basement membrane separating the two are less well defined than in wild-type mice
• after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice
• by week 8 after engraftment into a wild-type host, 1 of 4 ovaries contain Seroli cells tubule-like structures
|
• at E18.5, mutant ovaries lack a distinct cortex region
|
• by 8 weeks of engraftment into a wild-type host, remaining healthy follicles are larger than in wild-type mice
|
• when ovaries are transplanted into a wild-type host, follicles fail to progress beyond the pre-antral/early antral stages
|
• after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice
|
• at E18.5, mutant ovaries lack a distinct medulla region
|
small ovary
(
J:105944
)
• at E18.5, mutant ovaries are smaller than wild-type
|
ovary cyst
(
J:105944
)
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• seminiferous cords are present but interspersed with regions of disorganized cells where no cords are apparent
|
small testis
(
J:105944
)
|
• at E18.5, testes exhibit a reduced tunica albuginea
|
• lacrimal gland mesenchyme is insensitive to Bmp7 treatment unlike wild-type mesenchyme
• however, lacrimal gland epithelium proliferation in response to FGF is normal
|
renal/urinary system
duplex kidney
(
J:60834
)
• seen in 1 of 49 mice
|
bifid ureter
(
J:60834
)
• seen in 1 of 49 mice
|
cellular
• the ductus arteriosus connecting the aorta to the pulmonary artery fails to close in all newborns
|
• ovaries contain fewer germ cells that are found in clusters scattered throughout the ovary unlike in wild-type mice
|
• after 8 weeks of engraftment into a wild-type host, ovaries display oocyte degeneration or loss
|
• between E10.5 and E11.5, fewer than normal primordial germ cells migrate out of the hindgut resulting in fewer germ cells entering the developing gonads
• however, germ cell attractants are normally expressed
|
growth/size/body
ovary cyst
(
J:105944
)
• large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host
|
• at E18.5, no bursa membrane can be detected, unlike in wild-type ovaries
|