Description

Strain Information

Type Mutant Stock; Radiation Induced Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x +/+ sibling         (Female x Male)   19-MAR-09 Species laboratory mouse Generation F?+F8 (09-AUG-11) Generation Definitions   Donating Investigator Brian Popko,   University of Chicago

Description
Mice heterozygous for the radiation-induced Sprawling mutation of the cytoplasmic dynein heavy chain 1 gene (Dync1h1^Swl) are viable and fertile (the donating investigator reports that less than 50% of males breed successfully). Heterozygous mice display an early-onset hereditary proprioceptive sensory neuropathy with muscle spindle deficiency. Mice are distinguishable around one week after birth by the presence of hindlimb flexion during tail suspension, and around three to four weeks of age develop a typical unsteady gait characterized by jerky and wobbly locomotion. At rest, the hindlimbs are splayed and flexed forward and hindpaws are incapable of gripping structures. Defective proprioception is suggested as proprioceptive sensory neurons are severely compromised in the lumbar dorsal root ganglia of newborns and the H reflex is defective despite normal motor nerve function in the hindlimbs. Homozygous mice die in utero before embryonic day (E)8.5, indicating a late implantation or early gastrulation lethal phenotype. These Dync1h1^Swl mice may be useful in studying microtubule motor protein function in sensory neuron degeneration, specifically in proprioceptive sensory neurons.

Development
The radiation-induced Sprawling mutation (Swl) was first reported by Mr. Trevor Morris at the MRC Radiobiology Unit (Harwell, UK) in 1967 in mice used for an irradiation experiment several generations earlier. Mutant frozen embryos from the Mammalian Genetic Unit/Harwell (Oxfordshire, UK) were obtained by Dr. Brian Popko (The University of Chicago Illinois USA) and the mutation was identified as a nine base-pair deletion in exon 12 of the cytoplasmic dynein heavy chain 1 gene (Dync1h1) that affects residues 1040-1043 in the encoded protein. This mutation results in the change of four amino acids [glycine (GGC), isoleucine (ATA), valine (GTG), and threonine (ACT)] to an alanine (GCT) in the cargo-binding domain of the mature protein. Mice were maintained on the C3H/101 hybrid genetic background by breeding mutants with wild-type siblings. In 2008, these C3H/101-Swl mice were sent to The Jackson Laboratory (and assigned Stock No. 008393).

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

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.

Dync1h1^Swl/Dync1h1⁺

        involves: 101/H * C3H/HeH

• behavior/neurological phenotype
• abnormal resting posture
  • hind limbs are splayed out when mouse is at rest   (MGI Ref ID J:13469)
  • by 6 days of age impaired hind limb coordination is obvious   (MGI Ref ID J:13469)
• impaired limb coordination
  • hind limbs displace in a rapid vertical direction during locomotion   (MGI Ref ID J:13469)
  • mutants can be unquestionably distinguished from normal siblings at 12 days of age   (MGI Ref ID J:11963)
  • when the mouse is lifted the hind limbs flex to the trunk rather than extend as they would for a normal mouse; occasionally the fore limbs will also flex   (MGI Ref ID J:11963)
  • during forward motion hind limbs show stiffness on forward motion and move in a wider arc than do hind limbs of normal mice   (MGI Ref ID J:11963)
• jerky movement
  • during locomotion   (MGI Ref ID J:13469)
• growth/size phenotype
• abnormal postnatal growth
  • for several weeks growth rate is reduced compared to that of normal siblings   (MGI Ref ID J:13469)
• reproductive system phenotype
• male infertility
  • likely due to inability to mate   (MGI Ref ID J:11963)

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Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)

Neurobiology Research
Ataxia (Movement) Defects
Neurodegeneration
Neurodevelopmental Defects
Neuromuscular Defects

Research Tools
Neurobiology Research

Sensorineural Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dync1h1Swl
Allele Name		sprawling
Allele Type		Radiation induced
Common Name(s)		Swl;
Strain of Origin		(C3H/HeH x 101/H)F1
Gene Symbol and Name		Dync1h1, dynein cytoplasmic 1 heavy chain 1
Chromosome		12
Gene Common Name(s)		9930018I23Rik; AI894280; CMT20; DHC1; DHC1a; DNCH1; DNCL; DNECL; DYHC; Dnchc1; Dnec1; HL-3; Loa; MAP1C; RIKEN cDNA 9930018I23 gene; Swl; dynein heavy chain, retrograde transport; dynein, cytoplasmic 1; dynein, cytoplasmic, heavy chain 1; expressed sequence AI894280; legs at odd angle; mKIAA0325; p22; sprawling;
Molecular Note		The molecular mutation is a 9-bp deletion in exon 12 of the gene, that affects residues 1040-1043 in the encoded protein. This mutation results in the change of four amino acids [glycine (GGC), isoleucine (ATA), valine (GTG), and threonine (ACT)] to an alanine (GCT) in the cargo-binding domain of the mature protein. RT-PCR analysis indicates that mRNA expression of this allele is not altered in mutant mice, and immunohistochemistry experiments in mutant embryos shows that no gross differences in the level or localization of the encoded protein is evident. [MGI Ref ID J:131126]

Genotyping

Genotyping Information

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References

References provided by MGI

Selected Reference(s)

Chen XJ; Levedakou EN; Millen KJ; Wollmann RL; Soliven B; Popko B. 2007. Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci 27(52):14515-24. [PubMed: 18160659]  [MGI Ref ID J:131126]

Additional References

Dync1h1^Swl related

Brook GA; Duchen LW. 1990. End-plates, transmission and contractile characteristics of muscles without spindles in the hereditary sensory neuropathy of the Sprawling mouse. Brain 113(Pt 4):867-91. [PubMed: 2168780]  [MGI Ref ID J:130867]

Duchen LW. 1975. "Sprawling": a new mutant mouse with failure of myelination of sensory axons and a deficiency of muscle spindles. Neuropathol Appl Neurobiol 1:89-101.  [MGI Ref ID J:11963]

Duchen LW. 1974. A dominant hereditary sensory disorder in the mouse with deficiency of muscle spindles: the mutant Sprawling. J Physiol 237(2):10P-11P. [PubMed: 4274920]  [MGI Ref ID J:130870]

Duchen LW; Scaravilli F. 1977. Quantitative and electron microscopic studies of sensory ganglion cells of the Sprawling mouse. J Neurocytol 6(4):465-81. [PubMed: 894335]  [MGI Ref ID J:5867]

Duchen LW; Scaravilli F. 1977. The structure and composition of peripheral nerves and nerve roots in the Sprawling mouse. J Anat 123(3):763-75. [PubMed: 885789]  [MGI Ref ID J:5844]

Morris T. 1967. Sprawling (Swl). Mouse News Lett 37:29.  [MGI Ref ID J:13469]

Scaravilli F; Duchen LW. 1980. Electron microscopic and quantitative studies of cell necrosis in developing sensory ganglia in normal and Sprawling mutant mice. J Neurocytol 9(3):373-80. [PubMed: 7441297]  [MGI Ref ID J:130868]

Scaravilli F; Duchen LW. 1980. The development of sensory ganglion cells in normal and Sprawling mutant mice. J Neurocytol 9(3):363-71. [PubMed: 6449566]  [MGI Ref ID J:130869]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygotes may be bred to wildtype siblings. Homozygous mice die in utero. The donating investigator reports that the phenotype of heterozygous mice becomes more severe with backcrossing to inbred mice.
Mating System	Heterozygote x +/+ sibling         (Female x Male)   19-MAR-09
Diet Information	LabDiet® 5K52/5K67

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Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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