Mouse Igh locus

The mouse Igh locus is located on the telomeric end of chromosome 12 [91]. However, the orientation of the heavy chain locus is controversial. The order cen-tromere-VH-CH was originally proposed based on recombination frequencies [92] and an analysis of the Harwell translocation T(5 12)31H [91]. More recently, a mouse plasmacytoma (J558) carrying a translocation between the Igh locus on chromosome 12 and the c-myc locus on chromosome 15 has been fused with Chinese hamster cells by Erikson et al. [93]. These investigators concluded that the orientation of the mouse Igh locus is centromere-CH-VH. Additional studies will be necessary to resolve this point. 

SP2 region and CH, giving rise to a recombinant Igh locus having the VH and D segments of the a haplotype and the CH genes of the b parent (Brodeur and Ri-blet, in preparation). Therefore, the Igh haplotype of C.B/R5, VHa-Da-/-CHa (where 7 indicates the cross-over), provides direct evidence for the general organization of the mouse Igh locus. 

Fig. 4. Organization of the mouse Igh locus. The order of Vu gene families is based on Igh recombinant mouse strains [27] and deletion mapping studies [Brodeur. unpublished]. Approximate location of genetic cross-overs are designated by X. Distance (molecular and rccombinational) between or within V, gene families are unknown. The map position of the VnJ558 family is tentative (see text).

Fig. 1. Immunoglobulin gene rearrangement and expression. A highly simplified view of the mouse IgH locus is presented which is neither to scale nor are the full complements of gene segments depicted. The IgH enhancer is indicated by the symbol E.

Fig. 1. IgH locus of human and mouse. Constant region genes are indicated by closed boxes, switch regions by stippled boxes. The switch regions 5 of human al, e. and a2 are not precisely localized. In addition JH segments (vertical line with shorter lines for i/d), the D-Q52 segment ( ]) and areas that have not been overlapped (//) are indicated [11,95,96.31,32,34.35,40] (see also text).

The IgH locus encodes the antibody heavy chain, and the IgK and IgA, loci encode the light chains. Two Ig-deficient mice lines were constructed by inactivation of the murine IgH or the IgK loci using homologous recombination. Cross-breeding of the two mouse lines resulted in a double inactive mouse strain. 

Brodeur, P.H. Riblet, R. (1984). The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur. J. Immunol. 14,922-930. 

Using mouse-mouse hybrids and Robertsonian translocation markers, Hengart-ner et al. [86] confirmed that the expression of k light chains requires a locus on chromosome 6, whereas the expression of heavy chains required chromosome 12. The formal demonstration that the structural k and Igh loci reside on chromosomes 6 and 12, respectively, was obtained by the analysis of mouse-hamster hybrids using Southern blot hybridization [87,88], A similar approach was used by D Eustachio et al. [89] to assign the A locus to mouse chromosome 16. 

Enhancers are classically defined as DNA sequences which stimulate transcription of a linked gene from its authentic start site. This stimulation is observed with the enhancer placed upstream or downstream of the gene, at a distance of several thousand base pairs and in an orientation-independent manner (for a review see [80]). Enhancers were originally described in viruses but have since been identified in a number of cellular genes. The first cellular enhancer to be found was in the major intron of the mouse heavy chain locus [81-83] and subsequently in the mouse k [84,85] and human IgH loci [86]. 

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