Mouse Genome Informatics
hm1
    Frem1bat/Frem1bat
C57BL/6J-Frem1bat
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Frem1bat/Frem1bat mice display crytophthalmos and embryonic blebbing

vision/eye
• coloboma defects are associated with defects in formation of the conjunctiva
• coloboma defects are associated with cornea fibrosis
• coloboma defects are associated with absence of corneal epithelium leading to thinning of the cornea
• coloboma defects are associated with absence of corneal epithelium
• defects in the adhesion of the surface ectoderm and corneal stroma
• several mutants exhibit eyelid coloboma similar to that seen in Manitoba-oculo-tricho-anal syndrome, affecting only one part of the eyelid
• coloboma defects are associated with failure of eyelid formation, defects in formation of the conjunctiva, and absence of corneal epithelium leading to thinning of the cornea and fibrosis on the external face
• greater intercanthal distance
• have no true eyelids and the closed-eye appearance results from the presence of a pseudoblepharon that can be either unilateral or bilateral
• majority of mutants exhibit cryptophthalmos (J:200884)

limbs/digits/tail
• seen occasionally

renal/urinary system
• exhibit renal abnormalities
• about 20% of adults show unilateral renal agenesis

integument
• epidermis separates from the dermis below the level of the lamina densa creating blebs/blisters during embryonic development
• Background Sensitivity: blebbing phenotype is 100% penetrant on a C57BL/6J background but is only about 70% penetrant on a mixed C57BL/6J and C3H/NeJ background
• from E13.5, develop blebs located predominantly around the eyes and the sides of the head

craniofacial
• upper midface is raised along the proximal aspect of the metopic suture and is wider at the level of the coronal suture (J:177282)
• abnormalities include medial depression along the internasal suture and/or marked curvature of the nasal bones (J:177282)
• slightly shorter philtrum-columella height (J:200884)
• most mutants exhibit abnormal maxillary-premaxillary suture morphology
• mutants exhibit advanced fusion of the posterior frontal suture compared to wild-type mice
• 7 of 16 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia (J:177282)
• 7 of 16 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia (J:177282)
• reduction in snout length is inversely correlated with both cranial width and intercanthal distance (J:200884)

skeleton
• most mutants exhibit abnormal maxillary-premaxillary suture morphology
• mutants exhibit advanced fusion of the posterior frontal suture compared to wild-type mice
• mutants exhibit anterofrontal cranial deformation similar to metopic craniosynostosis and trigonocephaly
• mutants exhibit advanced fusion of the posterior frontal suture compared to wild-type mice, with fusion seen at postnatal day 28 compared to day 45 in controls

digestive/alimentary system
• 4 of 138 mutants exhibit anal prolapse, showing protrusion of the rectal epithelia and an immune infiltrate in exposed tissue
• the musculature of the anal sphincter is present in mutants with anal prolapse but is misplaced
• however, anorectal musculature appears normal

growth/size
• 7 of 16 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia (J:177282)
• 7 of 16 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia (J:177282)
• reduction in snout length is inversely correlated with both cranial width and intercanthal distance (J:200884)


Mouse Genome Informatics
ht2
    Frem1bat/Frem1+
C57BL/6J-Frem1bat
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• 42% of heterozygotes exhibit variable sutural abnormalities, including complete fusion, sutural asymmetry and advanced endocranial suture fusion
• 2 of 21 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia
• 2 of 21 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia

skeleton
• 42% of heterozygotes exhibit variable sutural abnormalities, including complete fusion, sutural asymmetry and advanced endocranial suture fusion
• mutants exhibit anterofrontal cranial deformation similar to metopic craniosynostosis and trigonocephaly, although less severe than seen in homozygotes

growth/size
• 2 of 21 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia
• 2 of 21 mutants exhibit varying degrees of midfacial asymmetry and/or midface hypoplasia

Mouse Models of Human Disease
OMIM IDRef(s)
Chromosome 9p Deletion Syndrome 158170 J:177282