Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names STOCK Dnahc5hlb612/JClo    (Changed: 23-MAY-13 ) Type Chemically Induced Mutation; Mutant Stock; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N4F2pN1 Generation Definitions

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.

Related Strains

Strains carrying other alleles of Dnah5

013612	C57BL/6J-Dnah5b2b002Clo/J
013619	C57BL/6J-Dnah5b2b016Clo/J
013686	C57BL/6J-Dnah5b2b1134Clo/J
013687	C57BL/6J-Dnah5b2b1154Clo/J
013663	C57BL/6J-Dnah5b2b601Clo/J

View Strains carrying other alleles of Dnah5     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Ciliary Dyskinesia, Primary, 3; CILD3

- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Tetralogy of Fallot; TOF

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dnah5^hlb612/Dnah5⁺

        involves: C57BL/6J

• respiratory system phenotype
• abnormal respiratory motile cilium morphology
  • mice exhibit reduced numbers of outer dynein arms in their tracheal cilia compared to in wild-type mice   (MGI Ref ID J:130755)

Dnah5^hlb612/Dnah5^hlb612

        involves: C57BL/6J

• mortality/aging
• complete lethality at weaning
  • mice that survive birth die between 3 and 4 weeks of age with normal or reversed body situs and domed heads indicative of hydrocephaly   (MGI Ref ID J:130755)
• partial perinatal lethality
  • mice with heterotaxia exhibit heart defects and die before or shortly after birth   (MGI Ref ID J:130755)
• growth/size phenotype
• heterotaxia
  • 40% of mice exhibit heterotaxia, 36% situs invertus and 24% situs solitus   (MGI Ref ID J:130755)
  • mice with heterotaxia exhibit heart defects and die before or shortly after birth   (MGI Ref ID J:130755)
• • left atrial isomerism
    • in one mouse   (MGI Ref ID J:130755)
  • left pulmonary isomerism
    • mice exhibit varying degrees of lung and bronchial tree left isomerism   (MGI Ref ID J:130755)
  • right atrial isomerism
    • in some mice   (MGI Ref ID J:130755)
  • situs inversus
    • 36% of mice exhibit situs inversus   (MGI Ref ID J:130755)
• cardiovascular system phenotype
• abnormal aortic arch morphology
  • in some mice   (MGI Ref ID J:130755)
• • interrupted aortic arch
    • in one mouse   (MGI Ref ID J:130755)
• abnormal heart morphology
  • mice exhibit a range of cardiac defects at varying degrees of penetrance including tetralogy of Fallot, transposition of the great arteries, a common atrioventricular canal, dextro- or meso-cardia, a common atrium, double outlet right ventricle, and septal defects   (MGI Ref ID J:130755)
• • abnormal heart development
    • some mice exhibit L ventricular loop with or without superior-inferior positioning of the ventricles   (MGI Ref ID J:130755)
    • some mice exhibit tetralogy of Fallot   (MGI Ref ID J:130755)
    • some mice exhibit a concordant vein and artery alignment in the great arteries   (MGI Ref ID J:130755)
  • atrioventricular septal defect
    • some mice exhibit a common or unbalanced atrioventricular canal committed to the right or left ventricle   (MGI Ref ID J:130755)
  • common atrioventricular valve
    • some mice exhibit a single atrioventricular valve of mitral morphology   (MGI Ref ID J:130755)
  • common atrium
    • some mice exhibit a common atrium   (MGI Ref ID J:130755)
  • dextrocardia
    • in some mice   (MGI Ref ID J:130755)
  • double outlet right ventricle
    • in some mice   (MGI Ref ID J:130755)
  • left atrial isomerism
    • in one mouse   (MGI Ref ID J:130755)
  • mesocardia
    • in some mice   (MGI Ref ID J:130755)
  • ostium secundum atrial septal defect
    • some mice exhibit secundum atrial septal defects   (MGI Ref ID J:130755)
  • right atrial isomerism
    • in some mice   (MGI Ref ID J:130755)
  • superior-inferior ventricles
    • in some mice   (MGI Ref ID J:130755)
  • transposition of great arteries
    • in some mice   (MGI Ref ID J:130755)
  • ventricular septal defect
    • in some mice   (MGI Ref ID J:130755)
• abnormal inferior vena cava morphology
  • inferior vena cava (IVC) abnormalities are observed in some mice including azygos continuation, interruption and duplication of the IVC   (MGI Ref ID J:130755)
• respiratory system phenotype
• abnormal respiratory motile cilium morphology
  • mice exhibit a wide range of tracheal cilia disorganization   (MGI Ref ID J:130755)
  • mice exhibit reduced numbers of outer dynein arms in their tracheal cilia compared to in wild-type mice   (MGI Ref ID J:130755)
• abnormal respiratory motile cilium physiology
  • tracheal cilia are immotile or slow and dyskinetic   (MGI Ref ID J:130755)
  • displacement of fluorescent beads deposited above the epithelia is reduced in velocity and directionality compared to in wild-type mice   (MGI Ref ID J:130755)
• left pulmonary isomerism
  • mice exhibit varying degrees of lung and bronchial tree left isomerism   (MGI Ref ID J:130755)
• digestive/alimentary phenotype
• abnormal digestive organ placement
  • in some mice the pancreas or the stomach are mal-positioned along the midline or the right side   (MGI Ref ID J:130755)
• hematopoietic system phenotype
• abnormal spleen morphology
  • in some mice the spleen is mal-positioned   (MGI Ref ID J:130755)
• • absent spleen
    • in some mice   (MGI Ref ID J:130755)
• nervous system phenotype
• hydroencephaly
  • mice that survive birth die between 3 and 4 weeks of age with domed heads indicative of hydrocephaly   (MGI Ref ID J:130755)
• liver/biliary system phenotype
• abnormal liver morphology
  • some mice exhibit a symmetric bilobed liver   (MGI Ref ID J:130755)
• craniofacial phenotype
• abnormal head morphology
  • mice that survive birth die between 3 and 4 weeks of age with domed heads indicative of hydrocephaly   (MGI Ref ID J:130755)
• immune system phenotype
• abnormal spleen morphology
  • in some mice the spleen is mal-positioned   (MGI Ref ID J:130755)
• • absent spleen
    • in some mice   (MGI Ref ID J:130755)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Heart Abnormalities

Developmental Biology Research
Internal/Organ Defects
      heart
      lung
      situs inversus

Internal/Organ Research
Heart Abnormalities
Lung Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dnah5hlb612
Allele Name		heart, lung and blood 612
Allele Type		Chemically induced (ENU)
Common Name(s)		Dnahc5del593; Mdnah5del267-859;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Dnah5, dynein, axonemal, heavy chain 5
Chromosome		15
Gene Common Name(s)		AU022615; CILD3; DLP5; DNAHC5; Dnahc5; Dnahc8; HL1; KTGNR; Mdnah5; Mutant line 1134; Mutant line 1154; Mutant line 1537; Mutant line 1565; PCD; b2b1134Clo; b2b1154Clo; b2b1537Clo; b2b1565Clo; expressed sequence AU022615;
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. [MGI Ref ID J:130755]

Genotyping

Genotyping Information

Genotyping Protocols

Dnahc5^hlb612, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tan SY; Rosenthal J; Zhao XQ; Francis RJ; Chatterjee B; Sabol SL; Linask KL; Bracero L; Connelly PS; Daniels MP; Yu Q; Omran H; Leatherbury L; Lo CW. 2007. Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia. J Clin Invest 117(12):3742-52. [PubMed: 18037990]  [MGI Ref ID J:130755]

Additional References

Dnah5^hlb612 related

Francis RJ; Chatterjee B; Loges NT; Zentgraf H; Omran H; Lo CW. 2009. Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway. Am J Physiol Lung Cell Mol Physiol 296(6):L1067-75. [PubMed: 19346437]  [MGI Ref ID J:164972]

Kim E; Tolhurst AT; Qin LY; Chen XY; Febbraio M; Cho S. 2008. CD36/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury. J Neurosci 28(18):4661-70. [PubMed: 18448643]  [MGI Ref ID J:134972]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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