SMAD family member 4 (coded by Smad4) is a member of a family of intracellular signaling mediators and plays a role as a tumor suppressor. SMAD4 is involved in growth control and transcriptional regulation during development by transmitting signals from the cell surface to the nucleus via the transforming growth factor &beta; (TGF&beta;) and bone morphogenic protein (BMP) signaling system. Mutations in the Smad4 gene have been associated with the rare connective tissue disorder Myhre Syndrome. Human patients may display craniofacial and skeletal deformities, intellectual disability and/or autism, hearing loss, thickened skin as well as cardiopulmonary problems. These Smad4-I499Vfl mice possess loxP sites flanking exon 12 of the Smad4 gene and an I499V missense mutation inserted immediately downstream of the second loxP site. After Cre-mediated recombination, the endogenous/wildtype exon 12 is removed and only the I499V point mutation is expressed in cre-expressing tissues. The I499V mutation is equivalent to the human I500V mutation found in Myhre Syndrome patients. Homozygous mice are viable and fertile with no overt phenotype. When Smad4-I499Vfl mice are bred to a Cre-recombinase (JAX Stock No. <a href="https://www.jax.org/strain/006054">006054</a>), the resulting heterozygous mice demonstrate liver and corneal fibrosis. These mice may be useful for studying Myhre Syndrome.

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Smad4-I499Vfl mice harbor a Cre-inducible I499V missense mutation in exon 12 of the Smad4 gene. After Cre-mediated recombination, the endogenous/wildtype exon 12 is removed and the mutant exon 12, harboring the I499V mutation, is expressed. These mice may be useful for studying Myhre Syndrome.

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