Disease relevance of Hm

• To facilitate the recognition of the homozygote of the reeler mutation (r1) at the embryonic stage, we introduced the chromosome carrying the autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross into the heterozygote of the reeler mutation, which is an autosomal recessive and located on the homologous chromosome [1].

High impact information on Hm

• The gene, designated Rmcfr, is dominant or semidominant and maps to chromosome 5; it is closely linked to the morphologic marker gene Hm [2].
• Mice bearing deletions presumably spanning the semidominant hammertoe locus (Hm) had no phenotype, suggesting that the classic allele is a dominant, gain-of-function mutation [3].
• In mice the dominant Hemimelic extra toes (Hx) and Hammertoe (Hm) mutations map to a homologous chromosomal region and cause similar limb defects [4].
• It is estimated that approximately 50% of the genome can be screened by scoring 50 fully informative gametes from a linkage cross of the MEV-Hm, -Sl, -CaJ stock for the combination of viral and visible markers [5].
• Three dominant visible markers, hammer-toe (Hm), steel (Sl), and caracul-J (CaJ), located on chromosomes 5, 10, and 15, respectively, have been introduced onto the MEV genetic background by repeated backcrosses to provide additional linkage markers [5].

Biological context of Hm

• Msx1 is close but not allelic to either Hm or Hx on mouse chromosome 5 [6].
• The mouse mutant Hammertoe (Hm) provides an abnormal system in which the pattern of cell death is specifically altered in the interdigital regions of the limb [7].
• Both the heterozygous rl embryos and non-carriers harbor the Hm locus and show the Hm phenotype as a deformity of the feet that can be recognized from the 15th day of gestation [1].
• Ectopic dermal ridge configurations on the interdigital webbings of Hammertoe mutant mice (Hm): another possible role of programmed cell death in limb development [8].

Anatomical context of Hm

• Both Hm/Hm and Hm/+ have a rudimentary extra digit in the postaxial area of the hindlimbs [9].
• The forelimbs of Hammertoe (Hm) mutant mouse fetuses were examined sequentially to clarify the relationship between the occurrence of abnormal programmed cell death (PCD) and the formation of phalangeal pads and dermal ridge patterns [8].
• METHODS: Relevant morphological features, with special emphasis on pads and dermal ridge configurations, were inspected on the exposed dermal surface of the forelimbs of adult Hm mutant mice [8].

Associations of Hm with chemical compounds

• Our preliminary data suggest that RA can also introduce cell death between digits 2, 3, 4, and 5 of the Hm mutant where there was no cell death to begin with [7].

Other interactions of Hm

• Hm and Hx are very tightly linked loci [6].
• Msx1 is expressed in the developing limb, while limb development is affected by the Hm and Hx mutations [6].
• Using this double heterozygous strain (+/rl-Hm/+), the homozygote of rl can be selected from littermates by the normal appearance of the feet [1].

Analytical, diagnostic and therapeutic context of Hm

• The purpose of the present work was to determine the effects of the hereditary malformation of Hammertoe mutant mice (gene symbol Hm) on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites of the epidermal ridge patterns (dermatoglyphics) [9].

References