STOCK Dnah5^hlb612/JClo

Stock number: 007863
Product name: Dnahc5^del593
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Mouse/Human Gene Homologs

Description

Homozygous mice carrying this ENU induced Dnah5^hlb612 mutation show situs inversus totalis with structural heart defects and cardiovascular anomalies along with abnormal respiratory cilia.

Detailed description

The ENU generated hlb612 allele contains an in-frame deletion in a dynein gene (Dnahc5) commonly associated with human primary ciliary dyskinesia (PCD). Thirty-six percent of homozygotes exhibit situs inversus totalis and hydrocephaly and die between 2-4 weeks of age. Forty percent of homozygotes die before or shortly after birth and exhibit heterotaxy with structural heart defects and cardiovascular anomalies including discordant atrioventricular and ventricular outflow situs, atrial/pulmonary isomerisms, artery alignment defects, interrupted inferior vena cava and dextrocardia. Electronmicroscopy reveals that the outer dynein arms of the respiratory cilia are greatly reduced in number. Respiratory cilia exhibit a wide variation in orientation. Cilia in the airway epithelia are immotile or slow and dsykinetic. Heterozygous mice do not have situs defects, however, respiratory cilia exhibit some reduction in the number of outer dynein arms.

This strain may be useful for studying left-right asymmetry and as a mouse model for primary ciliary dyskinesia.

Development

This phenotypic deviant was identified following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice (Stock No. 000664), in complex heart, lung, blood, and sleep disorders at the Mouse Heart, Lung, Blood, and Sleep Disorders (HLBS) Center at The Jackson Laboratory. G2 mice were transferred to the laboratory of Cecilia Lo at the NIH where the strain was backcrossed twice to C57BL/6J, three times to C3H/HeJ and two times to the consomic C57BL/6J-Chr 15^A/J/NaJ. The mutation was determined to be a 29.7Kb deletion spanning exons 7 to 17 of the Dnahc5 gene on chromosome 15. The deletion removed 593 amino acids from a region containing most of the heavy chain dynein interacting domain N1. Two males from the colony were transferred back to The Jackson Laboratory for sperm cryopreservation in 2008.

Allele

Symbol: Dnah5^hlb612
Name: heart, lung and blood 612
MGI accession ID: MGI:3722326
Generation method: Chemically induced (ENU)
Marker symbol: Dnah5
Marker name: dynein, axonemal, heavy chain 5
Chromosome: 15
Strain of origin: C57BL/6J
Molecular note: 29,755 base pairs containing exons 7 through 17 were deleted by ENU mutgenesis. This resulted in a 593 amino acid deletion in the protein and deletion of the DHC_N1 domain.