Mouse Genome Informatics
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    Chuktm1Mka/Chuktm1Mka
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes are born alive but die within 30 min after birth, probably due to cardiovascular malfunction

skeleton
• at E18, mutant skulls appear shorter and maldeveloped relative to wild-type skulls
• at birth, the mutant frontal bone is wider than that of wild-type mice
• newborn homozygotes exhibit a reduced interparietal bone
• newborn homozygotes exhibit a reduced parietal bone
• newborn homozygotes lack a portion of the presphenoid bone; in contrast, the basioccipital and basisphenoid bones appear grossly normal
• newborn homozygotes exhibit a significantly reduced vomer relative to wild-type newborns
• newborn homozygotes exhibit a reduced space between the pterygoid and jugal bones
• at birth, mutant hindpaws are completely devoid of phalanges; mutant forepaws display fusion of the first phalanges of digits III and IV and loss of the second and third phalanges
• the mutant xiphoid process fails to fuse and appears bifurcated
• at E16 and at birth, homozygotes display a shorter sternum that fails to fuse
• at E18, homozygotes exhibit smaller rib cages than wild-type mice
• at E18, many of the mutant cervical vertebrae appear fused
• at E18, many of the mutant sacral vertebrae appear fused
• at E18, many of the mutant sacral vertebrae appear small
• at E18, homozygotes exhibit smaller vertebral columns than wild-type mice
• newborn homozygotes exhibit defects in chondrocyte differentiation, with reduced concentration of collagen fibers and uncondensed nuclei in hypertrophied chondrocytes
• mutant digits are only partially mineralized
• at birth, mutant sterna display delayed ossification

craniofacial
• at E18, mutant skulls appear shorter and maldeveloped relative to wild-type skulls
• at birth, the mutant frontal bone is wider than that of wild-type mice
• newborn homozygotes exhibit a reduced interparietal bone
• newborn homozygotes exhibit a reduced parietal bone
• newborn homozygotes lack a portion of the presphenoid bone; in contrast, the basioccipital and basisphenoid bones appear grossly normal
• newborn homozygotes exhibit a significantly reduced vomer relative to wild-type newborns
• newborn homozygotes exhibit a reduced space between the pterygoid and jugal bones
• newborn homozygotes exhibit shorter maxillary and mandibular incisors with enlarged crowns; their anterior extents are enlarged and already exposed to the oral cavity at birth
• at E13, the mutant incisor tooth germ epithelium evaginates into the developing oral cavity rather than invaginating into underlying mesenchyme
• newborn homozygotes have molars with rounded and shallow cusps
• at E14.5-E15.5, when the primary enamel knot is histologically evident, mutant molar tooth germs exhibit a slight reduction in the size of enamel knots
• newborn homozygotes exhibit a reduced nasal septum and capsule
• at E18, homozygotes lack external ears

limbs/digits/tail
• at E18, homozygotes display rudimentary protrusions instead of normal external limbs; however, limb bones are only mildly truncated and of a relatively normal shape
• defective epidermal differentiation may impair production of morphogens by epidermal thickenings, such as the AER, contributing to aberrant limb patterning
• at birth, mutant digits are half the length of wild-type digits
• at birth, mutant hindpaws are completely devoid of phalanges; mutant forepaws display fusion of the first phalanges of digits III and IV and loss of the second and third phalanges
• at E14.5 and E16, mutant fore- and hindlimbs lack digit separation
• at E13, mutant forepaws fail to form distinct digits and display a webbed morphology as a result of reduced apoptosis in the interdigital region
• at E16, mutant forelimbs (but not hindlimbs) are shorter than wild-type forelimbs; however, no significant forelimb truncation is noted at E14.5
• at E16, mutant forelimbs are shorter than wild-type forelimbs
• at E18, homozygotes exhibit malformed tails

embryogenesis
• at birth, mutant placentae exhibit severe congestion of expanded blood vessels and sinuses on the maternal surface
• defective epidermal differentiation may impair production of morphogens by epidermal thickenings, such as the AER, contributing to aberrant limb patterning

hearing/vestibular/ear
• at E18, homozygotes lack external ears

digestive/alimentary system
• at E17, homozotes exhibit closure of the esophagus resulting from keratinocyte abundance

respiratory system
• newborn homozygotes exhibit a reduced nasal septum and capsule

growth/size
• newborn homozygotes exhibit shorter maxillary and mandibular incisors with enlarged crowns; their anterior extents are enlarged and already exposed to the oral cavity at birth
• at E13, the mutant incisor tooth germ epithelium evaginates into the developing oral cavity rather than invaginating into underlying mesenchyme
• newborn homozygotes have molars with rounded and shallow cusps
• at E14.5-E15.5, when the primary enamel knot is histologically evident, mutant molar tooth germs exhibit a slight reduction in the size of enamel knots
• newborn homozygotes exhibit a reduced nasal septum and capsule
• at E18, homozygotes lack external ears
• at E18, homozygotes exhibit an omphalocele where the gastrointestinal tract protrudes into the umbilical cord to form an external sac
• at birth, homozygotes are smaller than wild-type newborns and resemble E18 mutant fetuses
• notably, most major internal organs (including the heart, lungs, liver, kidneys, spleen, brain, and spinal cord), appear grossly normal

vision/eye
• newborn homozygotes show impaired development and differentiation of the cornea and conjunctiva, consistent with impaired expression of K12 (a marker for differentiated corneal epithelial cells) and K4 (a marker for conjunctival epithelial cells)
• at birth, the mutant conjunctiva is composed of cells with rounded nuclei instead of flattened differentiated cells, and continues to express high levels of K5, indicating nondifferentiation of basal cells
• absence of nuclear p50 staining and defective differentiation of the mutant conjunctiva suggest that the nuclear translocation of NF-kappaB is critical for the differentiation of the developing conjunctival epithelium
• at birth, the mutant corneal epithelial layer is poorly organized and consists of several layers of more rounded cells instead of two layers of flat cells of ectodermal origin
• at birth, the mutant corneal stroma is poorly organized and composed of several layers of rounded cells instead of several ordered layers of mesenchymal cells
• at birth, mutant eyes exhibit a multicellular layer of immature ectodermal cells that covers the cornea and fuses the cornea to the eyelid, preventing the sliding of upper and lower eyelids on the corneal surface
• although the eyes of newborn homozygotes appear wide open in the dissection microscope, they are in fact closed with underdeveloped eyelids

cellular
N
• in culture, MEFs obtained from at E13 homozygotes exhibit normal IKK activation and IkappaBalpha degradation in response to proinflammatory stimuli (J:54316)
• at E18, homozygotes show a complete block of keratinocyte differentiation, resulting in absence of a stratified, well-differentiated epidermis

integument
• at E14, mutant whisker follicles display an abnormal epithelium evagination, similar to that observed in mutant incisor tooth germ epithelium
• at E18, homozygotes show a complete block of keratinocyte differentiation, resulting in absence of a stratified, well-differentiated epidermis
• at E18, homozygotes exhibit absence of the stratum granulosum
• at E18, homozygotes exhibit hyperplasia of the stratum spinosum of the epidermis
• at E18, homozygotes exhibit increased thickness of the suprabasal layer as a result of increased cell proliferation
• at E16 and E18, homozygotes display a taut, smooth skin lacking the characteristic folds and wrinkles of wild-type skin
• mutant hindlimbs and tail are surrounded by a thick layer of skin that is abnormally fused to the skin cover of the body
• at E17, the mutant epidermis displays increased adhesiveness, with the highest concentration of proteoglycans in the area where the skin that normally surrounds the limb is fused to the skin surrounding the body

cardiovascular system
• at birth, mutant placentae exhibit severe congestion of expanded blood vessels and sinuses on the maternal surface

Mouse Models of Human Disease
OMIM IDRef(s)
Cocoon Syndrome 613630 J:195185