CHMU/LeJ

Stock number: 000293
Research areas: Dermatology Research, Developmental Biology Research, Neurobiology Research, Sensorineural Research

Description

This inbred mutant strain carries the congenital hydrocephalus (Foxc1^ch) and muted (Bloc1s5^mu) mutations characterized by light eyes at birth and a muted brown shade of fur, and various abnormalities including hydrocephalus.

Detailed description

Mice homozygous for the congenital hydrocephalus (Foxc1^ch) spontaneous mutation die at birth, probably from inability to breathe. Homozygous mutant mice have bulging hemorrhagic cerebral hemispheres and open eyelids, urogenital abnormalities, and severely abnormal skull, cervical vertebrae, sternum, laryngeal cartilages, and hyoid bone. The hydrocephalus may trace to lack of formation of subarachnoid space, which is first detectable in 11-day embryos. Most of the defects in the head region are probably secondary to the severe displacements created by the hydrocephalus. Mice homozygous for the muted spontaneous mutation (Bloc1s5^mu), maintained in repulsion with congenital hydrocephalus, have light eyes at birth and their fur is a muted brown shade, often with white underfur. Some have a balance defect, similar to that of pallid (Bloc1s6^pa). Homozygous mutant mice show head-tilting and loss of postural reflexes, due to absence of otoliths from the sacculus and utriculus of one or both ears. The bony labyrinth is normal; the mice are not deaf and do not circle. Mutant mice have prolonged bleeding times and a platelet storage pool deficiency (SPD) associated with abnormalities of the dense granules of the blood platelets.

Allele

Symbol: Bloc1s5^mu
Name: muted
MGI accession ID: MGI:1856106
Generation method: Spontaneous
Attributes: Hypomorph
Synonyms: mu
Marker symbol: Bloc1s5
Marker name: biogenesis of lysosomal organelles complex-1, subunit 5, muted
Marker synonyms: 1810074A19Rik; BLOC-1 subunit; BLOS5; HPS11; MU; Muted
Chromosome: 13
Strain of origin: STOCK t
Molecular note: An early transposon (Etn) insertion has been identified as the mutation underlying the phenotype in muted mice. Analysis of genomic DNA revealed an insertion into the third intron. 183 bp of Etn sequence has been incorporated into the mRNA , likely by the activation of cryptic splice sites within the Etn. This results in an in-frame insertion into the translated protein at position 106, predicting a 246 amino acid protein. A significant reduction in mRNA levels is observed.

Allele

Symbol: Foxc1^ch
Name: congenital hydrocephalus
MGI accession ID: MGI:1856705
Generation method: Spontaneous
Synonyms: ch; mf1^ch
Marker symbol: Foxc1
Marker name: forkhead box C1
Marker synonyms: ARA; ASGD3; Fkh1; fkh-1; FKHL7; FREAC3; FREAC-3; frkhda; IGDA; IHG1; IRID1; Mf1; Mf4; RIEG3
Chromosome: 13
Strain of origin: CBA x STOCK Tyr^c f
Molecular note: A transition point mutation at coding nucleotide 367 altered a C to a T in the coding region. This results in a stop codon in place of glutamine codon 123 (p.Q123*) in the sequences encoding the third helix of the WH domain. The authors predict that a truncated protein would be generated lacking DNA binding activity.