Disease relevance of Dh

• Although tibial hemimelia has been well documented in Dh mice, this study demonstrated a distinctive pattern of shortening of the tibia [1].
• Genetic study of this azygos trait will be useful for the study of lateral asymmetries in mammalian development and for the interpretation of venous heterotaxies (anomalous placement of veins) in the mouse that are found in association with mutations such as situs inversus viscerum (iv) and dominant hemimelia (Dh) [2].

High impact information on Dh

• In contrast, an incidence of 23.8% and 57.7% SMT was observed in BALB/c nu/+ heterozygotes, and in BALB/c nu/+, Dh/+ heterozygotes, respectively [3].
• A mouse gene, En-1, with an engrailed-like homeo box (class II) and flanking region maps to mouse chromosome 1 (near the dominant hemimelia gene) [4].
• Early during the process of limb initiation, Dh is involved in regulating the width of the limb bud, the mutation resulting in selective loss of anterior mesenchyme [5].
• The Dh gene functions in the initial stages of limb development and we suggest that these initial roles are linked to mechanisms that pattern gene expression in the AER [5].
• Cloning and sequencing of the mouse Gli2 gene: localization to the Dominant hemimelia critical region [6].

Biological context of Dh

• Dominant hemimelia and En-1 on mouse chromosome 1 are not allelic [7].
• Gli2 is expressed in Dh heterozygotes and homozygotes [6].
• The hindlimb malformations in adult mice heterozygous for the dominant gene Dominant hemimelia (Dh) and +/+ littermates were characterized in skeletons that had been fixed, stained, and cleared [1].
• On the other hand, among the F1 mice from the cross between DH (Dh/+) females and DDD males, there are no biased numbers of Dh genotype pups [8].
• Appearance of growth retardation was examined from the day of birth, and both growth-retarded and normally weaned Dh/+ males were genotyped for microsatellite marker loci spanning autosomes and the X Chromosome (Chr) [9].

Anatomical context of Dh

• However, levels of Thy 1.2 bearing cells, while reduced compared to either nu/+ or Dh/+ littermates, are significantly higher than nude mice in both Peyer's patches and lymph nodes [10].
• The hindlimb malformation of Dh/+ mice occurred in association with a reduced number (five) of lumbar vertebrae [1].
• The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen [11].
• The Dh gene induced skeletal deformities at the axial regions from the thorax to the tail [12].
• The lymph nodes are larger in Dh/+ mice than in normal +/+ littermates [13].

Associations of Dh with chemical compounds

• This is a consequence of synergism among three independent gene loci; that is, the Dh allele on chromosome (Chr) 1, the DDD allele on an X Chr-linked locus, and a Y Chr-linked locus in some strains [14].

Other interactions of Dh

• This shows that Dh is not a mutant allele of En-1 [7].
• The close linkage between the genes Dominant hemimelia (Dh) and peptidase-3 (Pep-3) has been determined in 65 informative matings with the recombination frequency of 3.8% [15].

References