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| This knockout of the (Alcam) gene displays retinal dysplasias and defasciculation of both retinal ganglion cell axons and motor axons and may be useful in studies of retinal development, axon fasciculation, immune cell function and cancer progression. | |||||||||||||||
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Description
Strain Information
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N8 (17-JUL-09) Donating Investigator Joshua Weiner, University of Iowa Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Embryonic spinal motor nerve bundles exhibit modest defects in fasciculation and, in some cases, abnormal axon trajectories form bridges or turn at right angles to adjacent nerves. However, adult motor function appears grossly normal. A similar defect is observed in retinal ganglion cell axons of the optic fiber layer, in which axons appear fanned-out and defasciculated with wide bundles. Homozygotes exhibit two types of retinal dysplasias characterized by photoreceptor cell evaginations or protrusions from the outer nuclear layer and retinal folding (invagination) inside the orb. The donating investigator indicates that this phenotype is less commonly observed on the C57BL/6 background. ALCAM is also believed to be important for immune system functioning, including T cell activation, and is a marker of tumor progression in numerous cancers. This mutant mouse strain may be useful in studies of retinal development, axon fasciculation, immune cell function and cancer progression.Development
A targeting vector was designed to insert the coding sequence of Enhanced Green Fluorescent Protein (EGFP) and a loxP-flanked neomycin resistance cassette in place of exon 1 of the targeted gene. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and chimeras were bred to generate heterozygotes and homozygotes. These mice were then crossed with a Cre-deleter strain (FVB/N-Tg(ACTB-cre)2Mrt) to excise the neo cassette leaving a single loxP site downstream of the EGFP in exon 1. The resulting pups were then backcrossed to C57BL/6 for at least 8 generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
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Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Alcamtm1Jawe/Alcamtm1Jawe
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
- vision/eye phenotype
- abnormal retina morphology (MGI Ref ID J:93205)
- in 75% of mutant eyes retinal dysplasia is seen with finger like projections of photoreceptor cells protruding into the outer nuclear layer and/or invagination of the retina without disrupting the cell layers
- dysplasia can be detected on P1
- abnormal photoreceptor outer segment morphology (MGI Ref ID J:93205)
- photoreceptor outer segments appear elongated and disorganized
- abnormal retinal ganglion layer morphology (MGI Ref ID J:93205)
- axons are loosely bundled and occasionally have aberrant trajectories however all exit the optic disc normally
- nervous system phenotype
- abnormal motor neuron innervation (MGI Ref ID J:93205)
- motor neurons are loosely bundled with some axons exiting the bundles at a right angle to the adjacent nerve and ending blindly or forming bridges to neighboring bundles
- abnormal photoreceptor outer segment morphology (MGI Ref ID J:93205)
- photoreceptor outer segments appear elongated and disorganized
This mouse can be used to support research in many areas including:
Developmental Biology Research
Eye Defects
Neurobiology Research
Fluorescent protein expression in neural tissue
Research Tools
Cancer Research
tumor immunology
Fluorescent Proteins
Sensorineural Research
Eye Defects
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Alcamtm1Jawe | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Joshua A Weiner | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | BEN-; | ||
| Mutation Made By | Joshua Weiner, University of Iowa | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Gene Symbol and Name | Alcam, activated leukocyte cell adhesion molecule | ||
| Chromosome | 16 | ||
| Gene Common Name(s) | AI853494; BEN; CD166; DM-GRASP; FLJ38514; MEMD; MGC71733; MGC:27910; MuSC; SC1; expressed sequence AI853494; | ||
| Molecular Note | Exon 1 was replaced by EGFP and loxP flanked neo via homologous recombination. Neo was removed via cre mediated recombination of the flanking loxP sites, resulting in increased GFP expression. Northern and immunohistochemical analysis confirmed the absence of RNA in adult brain and protein in E12 spinal cords. [MGI Ref ID J:93205] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Weiner JA; Koo SJ; Nicolas S; Fraboulet S; Pfaff SL; Pourquie O; Sanes JR. 2004. Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1. Mol Cell Neurosci 27(1):59-69. [PubMed: 15345243] [MGI Ref ID J:93205]
Additional References
Alcamtm1Jawe relatedDillon AK; Fujita SC; Matise MP; Jarjour AA; Kennedy TE; Kollmus H; Arnold HH; Weiner JA; Sanes JR; Kaprielian Z. 2005. Molecular control of spinal accessory motor neuron/axon development in the mouse spinal cord. J Neurosci 25(44):10119-30. [PubMed: 16267219] [MGI Ref ID J:102358]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry While maintaining a live colony, these mice are bred as homozygotes.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Production.
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Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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