Indian Hedge Hog, (Ihh) is one of three signaling molecules from the Hedgehog (Hh) gene family.[10] Genes of the Hh family, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh) and Ihh regulate several fetal developmental processes.[10] The Ihh homolog is involved in the formation of chondrocytes during the development of limbs.[10] The protein is released by small, non-proliferating, mature chondrocytes during endochondral ossification.[10] Recently, Ihh mutations are shown to cause brachydactyly type A1 (BDA1), the first Mendelian autosomal dominant disorder in humans to be recorded.[10][11] There are seven known mutations to Ihh that cause BDA1.[11] Of particular interest, are mutations involving the E95 residue, which is thought to be involved with proper signaling mechanisms between Ihh and its receptors.[11] In a mouse model, mice with mutations to the E95 residue were found to have abnormalities to their digits.[12]
Ihh may also be involved in endometrial cell differentiation and implantation. Studies have shown progesterone to upregulate Ihh expression in the murine endometrium, suggesting a role in implantation.[13] Ihh is suspected to be involved in the downstream regulation of other signaling molecules that are known to play a role in murine implantation.[14] Mouse models involving Ihh null mice demonstrated failure of attachment and decidualization.[14]
^Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE (July 1995). "Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog". Genomics. 28 (1): 44–51. doi:10.1006/geno.1995.1104. PMID7590746.
^ abcdeMa, G., Yu, J., Xiao, Y. et al. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res 21, 1343–1357 (2011). https://doi.org/10.1038/cr.2011.76
^ abcLodder EM, Hoogeboom AJM, Coert JH, de Graaff E. 2008. Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1. Am J Med Genet Part A 146A:2152–2154. doi:10.1002/ajmg.a.32441
^Gao, B., Hu, J., Stricker, S. et al. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature 458, 1196–1200 (2009). https://doi.org/10.1038/nature07862
^Qingxiang Wei, Eric D. Levens, Lilja Stefansson, Lynnette K. Nieman, Indian Hedgehog and Its Targets in Human Endometrium: Menstrual Cycle Expression and Response to CDB-2914, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 12, 1 December 2010, Pages 5330–5337, https://doi.org/10.1210/jc.2010-0637
^ abKathryn Smith, Redab Alnifaidy, Qingxiang Wei, Lynnette K. Nieman, Endometrial Indian hedgehog expression is decreased in women with endometriosis, Fertility and Sterility, Volume 95, Issue 8, 2011, Pages 2738-2741.e3, ISSN 0015-0282, https://doi.org/10.1016/j.fertnstert.2011.05.018.
Marigo V, Roberts DJ, Lee SM, et al. (1995). "Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog". Genomics. 28 (1): 44–51. doi:10.1006/geno.1995.1104. PMID7590746.
Chang DT, López A, von Kessler DP, et al. (1995). "Products, genetic linkage and limb patterning activity of a murine hedgehog gene". Development. 120 (11): 3339–53. doi:10.1242/dev.120.11.3339. PMID7720571.
Leek JP, Moynihan TP, Anwar R, et al. (1997). "Assignment of Indian hedgehog (IHH) to human chromosome bands 2q33→q35 by in situ hybridization". Cytogenet. Cell Genet. 76 (3–4): 187–8. doi:10.1159/000134545. PMID9186520.
Ito H, Akiyama H, Shigeno C, et al. (1999). "Hedgehog signaling molecules in bone marrow cells at the initial stage of fracture repair". Biochem. Biophys. Res. Commun. 262 (2): 443–51. doi:10.1006/bbrc.1999.1197. PMID10462495.
Bak M, Hansen C, Friis Henriksen K, Tommerup N (2001). "The human hedgehog-interacting protein gene: structure and chromosome mapping to 4q31.21→q31.3". Cytogenet. Cell Genet. 92 (3–4): 300–3. doi:10.1159/000056918. PMID11435703. S2CID32938414.
Gao B, Guo J, She C, et al. (2001). "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1". Nat. Genet. 28 (4): 386–8. doi:10.1038/ng577. PMID11455389. S2CID22572955.
McCready ME, Sweeney E, Fryer AE, et al. (2002). "A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved". Hum. Genet. 111 (4–5): 368–75. doi:10.1007/s00439-002-0815-2. PMID12384778. S2CID36346206.
