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Proximity of the Mep-1 gene to H-2D on chromosome 17 in mice
Abstract:
The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1b allele. Mouse strains in which meprin activity levels are normal are designated Mep-1a. Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1a F1 hybrids [C3H.A (KkDd) X C3H.OH (KdDk)] were backcrossed with Mep-1b C3H.OH (KdDk) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.
Insights
The Mep-1 gene influences meprin activity in mice. This study mapped the Mep-1 locus, finding it located near the H-2D and Tla genes on chromosome 17.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- The Mep-1 gene on mouse chromosome 17 regulates meprin, a kidney enzyme.
- Meprin activity varies between mouse strains, with Mep-1b alleles causing deficiency and Mep-1a alleles indicating normal activity.
- Previous studies localized Mep-1 telomeric to H-2D, near the Tla gene.
Purpose of the Study:
- To investigate the genetic linkage between the Mep-1 locus and the major histocompatibility complex (MHC).
- To precisely map the Mep-1 gene relative to known genetic markers like H-2D and Tla.
Main Methods:
- A linkage study involving backcrossing Mep-1a F1 hybrid mice with Mep-1b parents.
- Assaying progeny for H-2D markers, Pgk-2 isozymes, and meprin activity.
- Calculating recombination frequency between H-2D and Mep-1.
Main Results:
- A recombination frequency of 2.1% was observed between H-2D and Mep-1.
- The Mep-1 locus was mapped 2.1 crossover units telomeric to H-2D.
- The Mep-1 locus was found approximately 0.6 crossover units from the Tla gene.
Conclusions:
- The Mep-1 gene is located telomeric to H-2D and near Tla.
- The Mep-1 locus serves as a valuable new genetic marker for this region of the mouse genome.
- This mapping provides insights into the genetic organization of the mouse MHC region.