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the positional cloning work was underway, one of us (A. Russ) generated an independent mutation of Tbx15 by gene targeting in embryonic stem cells. The targeted allele, Tbx15LacZ, carries an IRES-LacZ-neo cDNA cassette that disrupts the open reading frame at codon 154 early in the T-box domain (Figure 3D). Animals heterozygous for the targeted allele are completely normal with regard to size, skeletal morphology, and hair-color distribution, but Tbx15LacZ/Tbx15LacZ homozygotes were noted to exhibit reduced body size and an abnormal craniofacial appearance identical to that caused by deH. We generated Tbx15LacZ/deH compound heterozygotes; on an Aw/at background, these animals exhibited the same abnormal restriction of dorsal pigmentation at P3.5 and expanded yellow flank area as described above for deH/deH animals (see Figure 2). These observations demonstrate that the pigmentary and craniofacial characteristics of deH are caused by loss of function for Tbx15."}

    craft-ca-core-dev

    {"project":"craft-ca-core-dev","denotations":[{"id":"T4473","span":{"begin":105,"end":110},"obj":"PR:000016145"},{"id":"T4474","span":{"begin":114,"end":118},"obj":"SO:0000704"},{"id":"T4475","span":{"begin":132,"end":141},"obj":"UBERON:0000922"},{"id":"T4476","span":{"begin":132,"end":152},"obj":"CL:0002322"},{"id":"T4477","span":{"begin":167,"end":173},"obj":"SO:0001023"},{"id":"T4478","span":{"begin":175,"end":180},"obj":"PR:000016145"},{"id":"T4479","span":{"begin":180,"end":184},"obj":"PR:000033987"},{"id":"T4480","span":{"begin":197,"end":201},"obj":"SO:0000243"},{"id":"T4481","span":{"begin":202,"end":206},"obj":"PR:000033987"},{"id":"T4482","span":{"begin":216,"end":224},"obj":"SO:0005853"},{"id":"T4483","span":{"begin":243,"end":261},"obj":"SO:0000236"},{"id":"T4484","span":{"begin":265,"end":270},"obj":"SO:0000360"},{"id":"T4485","span":{"begin":294,"end":300},"obj":"SO:0000417"},{"id":"T4486","span":{"begin":314,"end":321},"obj":"NCBITaxon:33208"},{"id":"T4487","span":{"begin":352,"end":358},"obj":"SO:0001023"},{"id":"T4488","span":{"begin":402,"end":410},"obj":"UBERON:0004288"},{"id":"T4489","span":{"begin":427,"end":431},"obj":"UBERON:0001037"},{"id":"T4490","span":{"begin":456,"end":461},"obj":"PR:000016145"},{"id":"T4491","span":{"begin":461,"end":465},"obj":"PR:000033987"},{"id":"T4492","span":{"begin":466,"end":471},"obj":"PR:000016145"},{"id":"T4493","span":{"begin":471,"end":475},"obj":"PR:000033987"},{"id":"T4494","span":{"begin":614,"end":619},"obj":"PR:000016145"},{"id":"T4495","span":{"begin":619,"end":623},"obj":"PR:000033987"},{"id":"T4496","span":{"begin":682,"end":689},"obj":"NCBITaxon:33208"},{"id":"T4497","span":{"begin":781,"end":786},"obj":"UBERON:0000180"},{"id":"T4498","span":{"begin":823,"end":830},"obj":"NCBITaxon:33208"},{"id":"T4499","span":{"begin":887,"end":897},"obj":"CHEBI:26130"},{"id":"T4500","span":{"begin":973,"end":978},"obj":"PR:000016145"}],"text":"While the positional cloning work was underway, one of us (A. Russ) generated an independent mutation of Tbx15 by gene targeting in embryonic stem cells. The targeted allele, Tbx15LacZ, carries an IRES-LacZ-neo cDNA cassette that disrupts the open reading frame at codon 154 early in the T-box domain (Figure 3D). Animals heterozygous for the targeted allele are completely normal with regard to size, skeletal morphology, and hair-color distribution, but Tbx15LacZ/Tbx15LacZ homozygotes were noted to exhibit reduced body size and an abnormal craniofacial appearance identical to that caused by deH. We generated Tbx15LacZ/deH compound heterozygotes; on an Aw/at background, these animals exhibited the same abnormal restriction of dorsal pigmentation at P3.5 and expanded yellow flank area as described above for deH/deH animals (see Figure 2). These observations demonstrate that the pigmentary and craniofacial characteristics of deH are caused by loss of function for Tbx15."}

    craft-ca-core-ex-dev

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