Mouse Genome Informatics
hm1
    Alx4tm1Rwi/Alx4tm1Rwi
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• >98% of homozygotes die perinatally of gastroschisis
• in ~2% of newborns, the ventral body wall defect heals spontaneously without herniation of the abdominal viscera; these rare survivors are fertile and give rise to viable offspring

craniofacial
• mutant newborns show a temporal delay in the formation (and hence, decreased size) of the parietal plate
• in contrast to wild-type, ossification of the parietal bone does not extend over the superior aspect of the skull
• skeletons of the rare homozygotes that survive to an age of 6 weeks, display a normal size parietal bone with normal cranial sutures

limbs/digits/tail
• polydactyly is associated with the formation of an ectopic anterior zone of polarizing activity (ZPA)
• all homozygotes show preaxial polydactyly or the presence of an extra digit on the anterior aspect of the limb
• every limb of every mutant newborn displays an extra digit; occasionally the extra digit represents a bifurcated first digit, and rarely two extra digits are present
• mutant limbs exhibit abnormal anterior-posterior patterning: the extra digits have posterior character (e.g. three phalanges)
• the extra digit arises from the anterior aspect of the limb bud
• no abnormalities are detected in more proximal skeletal elements of the limbs
• polydactyly is associated with the formation of an ectopic anterior ZPA

skeleton
• mutant newborns show a temporal delay in the formation (and hence, decreased size) of the parietal plate
• in contrast to wild-type, ossification of the parietal bone does not extend over the superior aspect of the skull
• skeletons of the rare homozygotes that survive to an age of 6 weeks, display a normal size parietal bone with normal cranial sutures

growth/size
• the herniation is caused by complete absence of ventral abdominal wall musculature, and is associated with reduced skin thickness
• >98% of homozygotes exhibit gastroschisis, a ventral body wall defect resulting in herniation of abdominal contents
• in most cases, the ventral body wall defect is first noted at ~E15.5 and herniation occurs in utero; occasionally, herniation occurs at birth

embryogenesis
• polydactyly is associated with the formation of an ectopic anterior zone of polarizing activity (ZPA)


Mouse Genome Informatics
hm2
    Alx4tm1Rwi/Alx4tm1Rwi
involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• >98% of homozygotes die perinatally of gastroschisis
• in ~2% of newborns, the ventral body wall defect heals spontaneously without herniation of the abdominal viscera; these rare survivors are fertile and give rise to viable offspring

craniofacial
• mutant newborns show a temporal delay in the formation (and hence, decreased size) of the parietal plate
• in contrast to wild-type, ossification of the parietal bone does not extend over the superior aspect of the skull
• skeletons of the rare homozygotes that survive to an age of 6 weeks, display a normal size parietal bone with normal cranial sutures

skeleton
• mutant newborns show a temporal delay in the formation (and hence, decreased size) of the parietal plate
• in contrast to wild-type, ossification of the parietal bone does not extend over the superior aspect of the skull
• skeletons of the rare homozygotes that survive to an age of 6 weeks, display a normal size parietal bone with normal cranial sutures

growth/size
• >98% of homozygotes exhibit gastroschisis, a ventral body wall defect resulting in herniation of abdominal contents
• the herniation is caused by complete absence of ventral abdominal wall musculature, and is associated with reduced skin thickness
• in most cases, the ventral body wall defect is first noted at ~E15.5 and herniation occurs in utero; occasionally, herniation occurs at birth


Mouse Genome Informatics
ht3
    Alx4tm1Rwi/Alx4+
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• heterozygotes are apparently normal and do NOT display polydactyly


Mouse Genome Informatics
ht4
    Alx4tm1Rwi/Alx4+
involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• notably, heterozygous F1 progeny of a 129/Sv x C57BL/6J mating display hindlimb polydactyly


Mouse Genome Informatics
cx5
    Alx4tm1Rwi/Alx4+
Bmp4tm1Blh/Bmp4+

involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• all double heterozygotes exhibit ectopic anterior digits only on the hindlimbs
• extra digit extends from a duplicated metatarsal
• extra digits are triphalangeal
• post axial "nubbins" also seen on the forelimbs of 80% of heterozygotes


Mouse Genome Informatics
cx6
    Alx1tm1Crm/Alx1tm1Crm
Alx4tm1Rwi/Alx4tm1Rwi

involves: 129S6/SvEvTac * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• double homozygous mutants show a midline fusion defect that results in cleft face

limbs/digits/tail
• double homozygous mutants have an increased number of digits (usually 7 on the hindlimb, and 6 or 7 on the forelimb) with variable expressivity
• double homozygous mutants display tibial reduction (hemimelia) with variable expressivity
• in contrast, single mutant mice never display hemimelia

skeleton
• double homozygous mutants display tibial reduction (hemimelia) with variable expressivity
• in contrast, single mutant mice never display hemimelia
• double homozygous mutants exhibit a unique sternal phenotype not present in either single mutant: all homozygotes have a split sternum
• double homozygotes show abnormal rib insertions
• some double homozygotes display a reduction in the number of ribs attached to the sternum

nervous system
• all double homozygous mutants display exencephaly

growth/size
• double homozygous mutants show a midline fusion defect that results in cleft face
• at E19.5, double homozygous mutants show severe abdominal wall defects and herniation of abdominal contents


Mouse Genome Informatics
cx7
    Alx1tm1Crm/Alx1+
Alx4tm1Rwi/Alx4+

involves: 129S6/SvEvTac * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• double heterozygotes appear phenotypically normal


Mouse Genome Informatics
cx8
    Alx1tm1Crm/Alx1+
Alx4tm1Rwi/Alx4tm1Rwi

involves: 129S6/SvEvTac * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• mutant mice show a reduction in the size of the frontal, parietal, occipital and temporal plates of the skull
• mandibular reduction is mainly restricted to the region anterior to the alveolar process that surrounds the molars
• mutant mice exhibit a cleft palate with full penetrance but variable expressivity
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum
• mutant mice exhibit novel craniofacial defects including a midline fusion defect that results in cleft face

limbs/digits/tail
• mutant mice display a polydactyly phenotype that is intermediate in severity compared to single Alx4tm1Rwi mutant mice and double homozygous null mice
• mutant mice display tibial reduction; however, hemimelia is less severe in comparison to the double mutant phenotype

respiratory system
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum

skeleton
• mutant mice show a reduction in the size of the frontal, parietal, occipital and temporal plates of the skull
• mandibular reduction is mainly restricted to the region anterior to the alveolar process that surrounds the molars
• mutant mice display tibial reduction; however, hemimelia is less severe in comparison to the double mutant phenotype

vision/eye
• mutant mice are born with open eyes

digestive/alimentary system
• mutant mice exhibit a cleft palate with full penetrance but variable expressivity

growth/size
• mutant mice exhibit a cleft palate with full penetrance but variable expressivity
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum
• mutant mice exhibit novel craniofacial defects including a midline fusion defect that results in cleft face
• at E19.5, mutant mice show severe abdominal wall defects and herniation of abdominal contents


Mouse Genome Informatics
cx9
    Alx1tm1Crm/Alx1tm1Crm
Alx4tm1Rwi/Alx4+

involves: 129S6/SvEvTac * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• mandibular reduction is mainly restricted to the region anterior to the alveolar process that surrounds the molars
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum
• mutant mice show a midline fusion defect that results in cleft face

respiratory system
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum

skeleton
• mandibular reduction is mainly restricted to the region anterior to the alveolar process that surrounds the molars

nervous system
• all double homozygous null mice display exencephaly

growth/size
• mutants that carry three mutant alleles in any combination show cleft face associated with failure to fuse the cartilages of the nasal septum
• mutant mice show a midline fusion defect that results in cleft face