Mouse Genome Informatics
hm
    Lrp6Cd/Lrp6Cd
A-Lrp6Cd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• about 16.4% die shortly after birth with exencephaly (J:13045)
• folic acid supplementation prolongs survival (J:58433)
• about 23.6% are pre-implantation lethals (J:13045)
• about 24% die after implantation

growth/size
• mutants are significantly smaller at birth and remain so thereafter
• about 28% of mutants are 1/2 to 1/3 the size of control littermates (J:13045)
• about 40% of the animals successfully complete neural tube closure but are runted (J:58433)
• the small mutants appear growth retarded and smaller around 16-20 days of age

nervous system
• variable penetrance of exencephaly; mutants with exencephaly are normal sized (J:13045)
• 20% exhibit exencephaly (J:58433)
• the neural folds in the mesencephalon remain separated in the midline and splay over the skull base (J:58433)
• females more than males display exencephaly (J:58433)
• folic acid supplementation reduces the risk of exencephaly by as much as 55%; females are more responsive to the folic acid than males (J:58433)
• mice display cranial but not spinal neural tube defects (J:101423)

skeleton
• cranial bones are thinner
• mutants exhibit an inter-orbital pinched appearance of the frontals
• 95% have abnormal caudal vertebrae (J:13045)
• seen on a rare occasion (J:13045)
• misshapen or fused vertebrae (J:101423)
• many caudal vertebrae are shortened, some so much that they appear as bone fragments
• 68.75% have lumbar abnormalities (J:13045)
• 26.5% have sacral abnormalities
• delayed skull ossification
• slower closure of sutures

craniofacial
• cranial bones are thinner
• mutants exhibit an inter-orbital pinched appearance of the frontals
• tooth germs that give rise to the third molars reach the cap stage but do not invaginate to form a bell
• regression of the third molars begins earlier and lasts longer, beginning on the 5th day instead of the 6th day in controls
• molar development is slightly delayed such that at P3, when the enamel organ has reached the bud stage in wild-type, it is still in the early bud stage in mutants; this difference persists up to P8
• 4 of 17 mutants have bent noses; the nasals are not aligned with the medial suture of the paired frontals
• since there are no erupted lower incisors, there is continous growth and inward curving of the upper incisors; the teeth force themselves against the palate, cause ulcerations, inanition, and death (J:13045)
• lower incisors are greatly reduced (J:12999)
• crown cusp pattern of the molars is abnormal
• all mutants (30 of 30) show absence of at least one third molar (J:12998)
• most mutants have no third molars at all; only 3 of 30 mutants have just one third molar missing (J:12998)
• males are more severely affected than females (J:12998)
• however, upper and lower jaws are almost equally affected, with no differences between right and left (J:12998)
• all molars are significantly reduced in size; however, the greatest size reduction is confined to the third molars which tend to be absent (J:12998)
• the first molars are moderately reduced while the second molars are considerably reduced in size (J:12999)
• reduced and/or unerupted lower incisors (J:13045)
• small mutants have elongate and pointed heads
• occasionally small mutants have inclined pinnae

limbs/digits/tail
• 95% have abnormal caudal vertebrae (J:13045)
• seen on a rare occasion (J:13045)
• misshapen or fused vertebrae (J:101423)
• many caudal vertebrae are shortened, some so much that they appear as bone fragments
• crooked tail

vision/eye
• occurs sometimes

behavior/neurological
• 58% of small mutants exhibit nervous head movement

hearing/vestibular/ear
• occasionally small mutants have inclined pinnae

respiratory system
• 4 of 17 mutants have bent noses; the nasals are not aligned with the medial suture of the paired frontals

embryogenesis
• irregular somites at E14
• smaller somites with reduced intervertebral spaces

integument
• the coat of some small mutants appears to have an abnormal texture which makes them appear ungroomed
• almost naked tail (J:12999)
• sparse hairs on the tail; the hairs are short and bristle-like (J:13045)
• coats of some small mutants appears thin (J:13045)
• skin on the tail lacks the proper tail rings (J:12999)
• small mutants exhibit irregular, discontinuous tail rings (J:13045)

Mouse Models of Human Disease
OMIM IDRef(s)
Neural Tube Defects, Folate-Sensitive 601634 J:58433 , J:101423