Mouse Genome Informatics
hm
    Chuktm1Ver/Chuktm1Ver
involves: 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• although homozygotes develop to term, they are stillborn or die shortly after birth

limbs/digits/tail
• at birth, all long bones of mutant limbs appear to be formed with no major defects in the pattern and size of proximal limb elements; in contrast, the curvature of distal limb elements is abnormal
• in mutants, upper limb (humerus) and middle limb elements (radius, and ulna) fail to emerge out of the body trunk, resuting in a bottle-shaped body morphology
• as early as E12.5, mutant limb buds are short and dumpy
• in newborn homozygotes, most distal limb elements exhibit retarded and aberrant phalanx formation
• at birth, mutant hindlimbs together with the curled tail are embedded in thick skin
• at birth, all four mutant limbs are barely protruding and appear to be shortened
• as early as E12.5, homozygotes exhibit a curled, fused tail

skeleton
• newborn homozygotes exibit abnormal craniofacial bone morphology
• in newborn homozygotes, most distal limb elements exhibit retarded and aberrant phalanx formation
• mutant ribs display a kinky fusion to the sternum
• homozygotes have a broader sternum exhibiting incomplete and asymmetric ossification with split sternebra 6
• mutant sternal bands are shorter and broader with an abnormal kinked shape but remain well fused and functional
• incomplete and asymmetric ossification

craniofacial
• newborn homozygotes exibit abnormal craniofacial bone morphology
• newborn homozygotes exhibit a cleft secondary palate
• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed
• newborn homozygotes exhibit smaller and distorted incisors

digestive/alimentary system
• newborn homozygotes exhibit a cleft secondary palate
• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed
• newborn homozygotes display a shorter and narrower intestine than wild-type mice
• newborn homozygotes have a significantly smaller stomach than wild-type newborns

liver/biliary system
• all newborn homozygotes display an expanded bladder

embryogenesis
• as early as E12.5, mutant limb buds are short and dumpy

homeostasis/metabolism

cellular
• mutant MEFs exhibit significantly reduced NF-kappaB activation upon induction with TNF or IL-1

growth/size/body
• newborn homozygotes exhibit a cleft secondary palate
• mutant bilateral palate shelves remain unfused, allowing the more dorsal lying vomer and presphenoid to be exposed
• newborn homozygotes exhibit smaller and distorted incisors
• at E18, homozygotes exhibit retarded umbilical hernia withdrawal relative to wild-type mice

endocrine/exocrine glands
• all newborn homozygotes display an expanded bladder

integument
• newborn homozygotes display a reduced number of hair follicles, as mutant follicles fail to invaginate deeply into dermis
• newborn homozygotes have an abnormally tense and sticky skin that fails to attach to the limbs and thus covers the body like a bag
• the epidermis of newborn homozygotes displays a block in stratum corneum differentiation and complete absence of squames
• newborn homozygotes lack identifiable epidermal granular cells with distinctive keratohyalin granules; instead, several layers of flattened cells are present on the surface of mutant skin
• newborn homozygotes exhibit significantly increased suprabasal cell density relative to wild-type mice
• mutant suprabasal cells fail to differentiate into granular cells and cornified cells, as shown by significantly reduced expression of filaggrin and loricrin in mutant skin
• newborn homozygotes exhibit absence of the superficial keratinized squamous layer of the epidermis

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