C3H;101-Dync1h1^Swl/PopJ

Stock number: 008393
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

These mice harbor the radiation-induced Sprawling mutation of the cytoplasmic dynein heavy chain 1 gene (Dync1h1^Swl) and may be useful in studying microtubule motor protein function in sensory neuron degeneration, specifically in proprioceptive sensory neurons.

Detailed 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).

Allele

Symbol: Dync1h1^Swl
Name: sprawling
MGI accession ID: MGI:1861136
Generation method: Radiation induced
Synonyms: Swl
Marker symbol: Dync1h1
Marker name: dynein cytoplasmic 1 heavy chain 1
Marker synonyms: 9930018I23Rik; CDCBM13; CMT2O; DHC1; DHC1a; Dnch1; Dnchc1; DNCL; Dnec1; DNECL; DYHC; dynein heavy chain, retrograde transport; HL-3; Loa; MAP1C; mKIAA0325; p22; SMALED1; Swl
Chromosome: 12
Strain of origin: (C3H/HeH x 101/H)F1
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.