This spontaneous point mutation causes a less severe phenotype than null mutants or other defined spontaneous mutations of this gene and is valuable for assessing the role of this gene in nervous system development and possibly congenital heart defects associated with some cases of Down syndrome.Read More +
Dscam3J, a point mutation causing an R1018P amino acid substitution in the second fibronectin domain, causes a less severe phenotype than Dscam2J, Dscamdel17, or Dscam targeted null mutants. The phenotype of Dscam null mutants varies with genetic background and includes respiratory distress, associated perinatal lethality, changes in C4 ventral root and pre-inspiratory neuron signaling, and an abnormal response to hypercapnia. Dscam3J homozygotes display kyphosis, domed skull, muscle stiffness, and less difficulty in the righting response than is found in Dscam2J homozygotes, which have a truncation in the extracellular domain of this protein. Dscam3J homozygotes have enlarged central and lateral ventricles of the brain.
Characterization of the retina shows that, similar to Dscam2J homozygotes, Dscam3J homozygotes have expanded inner plexiform, inner nuclear and retinal ganglion cell layers, but, distinct from Dscam2J homozygotes, the inner nuclear layer is evenly laminated. The retinal ganglion cells have defects in arborization and soma spacing, but the dopaminergic amacrine cells have reduced defects in arborization and soma spacing compared with those of the retinas of Dscam2J homozygotes. Retinas of Dscam3J homozygotes also have increased incidence of juxtaposed dopaminergic amacrine cells, occasional loose fasciculation of dopaminergic amacrine cell neurites, and increased numbers of bNOS amacrine cells, which also have abnormal spacing and appear hypertrophied, but the severity of these defects is less severe than the defects caused by other Dscam mutant alleles. The defects in neurite lamination, laminar specificity of type 2 and type 6 cone bipolar cells, and the disrupted targeting of retinal ganglion cell axons to the dorsal lateral geniculate nucleus that are found in Dscam2J and other Dscam mutant homozygotes are not distinct phenotypes in Dscam3J homozygotes. Subcellular localization of DSCAM protein from Dscam3J homozygotes shows increased retention in the cell bodies in the retinal ganglion cell layer consistent with a model of mis-localization of this mutant protein. (See Schramm et al., 2013 for more detail.)
The Dscam3J arose spontaneously in the strain C3SnSmn.CB17-Prkdcscid/J in 1994 when that strain was at generation N10F48. The mutant subline was backcrossed twice to C3HeB/FeJ to breed out the Prkdcscid mutation and then maintained by sibling intercrossing. In 2013 this mutant subline was again backcrossed to C3HeB/FeJ to address a breeding slump and subsequently maintained by sibling intercrossing.
|Allele Name||3 Jackson|
|Allele Synonym(s)||DSCAMR1018P; nm2122|
|Gene Symbol and Name||Dscam, DS cell adhesion molecule|
|Strain of Origin||C3SnSmn.Cg-Prkdcscid/J|
|Molecular Note||A spontaneous G-to-C point mutation (C-to-G on forward strand) results in the amino acid substitution of arginine with proline at position 1018 (p.R1018P). Western blot analysis confirmed normal protein expression levels.|
When using the C3(Cg)-Dscam3J/GrsrJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #006046 in your Materials and Methods section.