Mouse Genome Informatics
hm
    Msx2tm1Rilm/Msx2tm1Rilm
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c) or (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
N
• homozygotes are alive when kept on a protein-rich liquid diet (J:61509)

behavior/neurological
N
• homozygotes are not ataxic (J:61509)
• between 3 weeks and 2 months of age, mutants exhibit generalized seizures characterized by 3-min periods of often unilateral, myotonic limb extension, after which the mice recover

craniofacial
• at E18, homozygotes display a delay in frontal bone growth and interparietal and supraoccipital bone ossification
• in adult homozygotes, the mutant calvarium contains a significant midline foramen spanning the frontal bones
• frontal bone thickness is decreased anterior to the foramen
• the interparietal bone appears small and misshapen relative to wild-type
• the supraoccipital bone appears small and misshapen relative to wild-type
• mutant incisor teeth are misaligned
• ameloblasts form, but undergo a progressive, TUNEL-negative degeneration after P1
• by P9, the ameloblast layer contains cellular debris and inflammatory cells, and only small amounts of enamel have accumulated
• mutant molars display severe degeneration, resulting in inability to chew solid food
• at E16.5, homozygotes show a small reduction in enamel organ volume
• at E17.5, the stellate reticulum is reduced in volume
• by P1, only a compact accumulation of epithelial cells is found in the mutant intercuspal regions; these cells abut the ameloblast layer and the stratum intermedium becomes indistinguishable
• mutant incisor teeth are brittle

endocrine/exocrine glands
• ~30% of mutant females exhibit abnormal mammary development (J:61509)
• in female neonates, mammary epithelial development arrests at the mammary sprout stage, developmentally equivalent to E16.5 (J:61509)

limbs/digits/tail
• the mutant femur length is 83% that of wild-type
• the mutant tibia length is 88% that of wild-type

skeleton
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased
• in mutants, axial and appendicular skeletal lengths are reduced relative to wild-type
• the mutant femur length is 83% that of wild-type
• the mutant tibia length is 88% that of wild-type
• the cell size of hypertrophic chondrocytes is reduced resulting in a smaller growth plate
• in mutants, axial and appendicular skeletal lengths are reduced relative to wild-type
• at E18, homozygotes display a delay in frontal bone growth and interparietal and supraoccipital bone ossification
• in adult homozygotes, the mutant calvarium contains a significant midline foramen spanning the frontal bones
• frontal bone thickness is decreased anterior to the foramen
• the interparietal bone appears small and misshapen relative to wild-type
• the supraoccipital bone appears small and misshapen relative to wild-type
• mutant incisor teeth are misaligned
• the osteoblast defect appears to predominate as mutants are osteopenic
• at P30, mutant tibias show reduced cortical bone thickness
• by P30, cancellous bone is reduced
• by P30, the numbers of resting, proliferative and hypertrophic chondrocytes are decreased
• by P30, homozygotes exhibit osteochondrodystrophy i.e. abnormal cartilage and endochondral bone formation
• in homozygotes, BrdU-labelled osteoprogenitors in osteogenic fronts are reduced by 46% and 51% at P0 and P4, respectively

nervous system
N
• homozygotes display no cerebral phenotype (J:61509)
• between 3 weeks and 2 months of age, mutants exhibit generalized seizures characterized by 3-min periods of often unilateral, myotonic limb extension, after which the mice recover
• homozygotes show a reduction in the number of cerebellar lobules
• homozygotes show a lamination failure of the PCL
• homozygotes show a lamination failure of the IGL
• Purkinje cells are present but fail to coalesce into a discrete PCL, and the IGL is not compacted
• mutants display disorganized hemispheral and anterior vermal lobules
• the mutant vermis lacks a posterior lobule corresponding to the pyramis
• the mutant vermis is hypoplastic

hematopoietic system
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased

immune system
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased

integument
N
• mutant pups show normal whisker pad histology, innervation, and whisker-related pattern formation along the trigeminal pathway (J:73670)
• ~30% of mutant females exhibit abnormal mammary development (J:61509)
• in female neonates, mammary epithelial development arrests at the mammary sprout stage, developmentally equivalent to E16.5 (J:61509)
• beginning at P14, homozygotes loose their pelage, becoming nude except for the snout and peri-orbital regions
• pelage regrowth occurs, but premature loss also occurs for the second coat, followed again by regrowth; thereafter, hair loss is patchy
• hair loss is temporally associated with premature entry into the catagen phase of the hair growth cycle
• at P5, mutant whiskers are curly
• at P5, mutant whiskers appear short and stubby

hearing/vestibular/ear

growth/size/body
• ameloblasts form, but undergo a progressive, TUNEL-negative degeneration after P1
• by P9, the ameloblast layer contains cellular debris and inflammatory cells, and only small amounts of enamel have accumulated
• mutant molars display severe degeneration, resulting in inability to chew solid food
• at E16.5, homozygotes show a small reduction in enamel organ volume
• at E17.5, the stellate reticulum is reduced in volume
• by P1, only a compact accumulation of epithelial cells is found in the mutant intercuspal regions; these cells abut the ameloblast layer and the stratum intermedium becomes indistinguishable
• mutant incisor teeth are brittle

Mouse Models of Human Disease
OMIM IDRef(s)
Parietal Foramina; PFM 168500 J:61509