Mice heterozygous for the csp1 ENU-induced mutation possess a C to A mutation within intron 6 of the PR domain containing 16 (Prdm16) gene, resulting in an absent exon 7 and early termination within exon 8. Csp mice produce a truncated Prdm16 protein. These mice may be useful for studying palate formation and clefting disorders, such as non-syndromic CP (NSCP) and PRS-like CP.
David Beier, Harvard
Mice heterozygous for the csp1 ENU-induced mutation, are viable, fertile, and normal in size. Homozygous mutants exhibit the cleft palate (CP) phenotype and perinatal lethality with respiratory failure. The occurrence of the CP phenotype in homozygous csp1 mice drops to 9% after backcrossing onto the C57BL/6J background for four generations, although 93% of these mice still die shortly after birth and still exhibit respiratory failure. Approximately 6% of heterozygous mutant mice exhibit the (CP) phenotype. These csp1 mice possess a C to A mutation within intron 6 of the PR domain containing 16 (Prdm16) gene, resulting in vairable absence of exon 7 and early termination within exon 8. It is unclear if this truncated PRDM16 protein is stable in csp1. The CP phenotype of these csp1 mice is exhibited by micrognathia and failed palate shelf elevation due to physical obstruction by the tongue, resembling human Pierre Robin sequence (PRS)-like cleft secondary palate. Abnormalities in other non-craniofacial structures are evident including choroid plexus hypoplasia in the brain ventricles, reduction in heart ventricle and lung sizes, and abnormal retinal folds. This strain may be useful for studying palate formation and clefting disorders, such as non-syndromic CP (NSCP) and PRS-like CP.
Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder BALB/c mice, mutant mice having a wide cleft of the secondary palate and abnormal positioning and morphology of the tongue were identified. A mutagenesis screen confirmed a C to A mutation within intron 6 of the PR domain containing 16 (Prdm16) gene, resulting in variable absence of exon 7 and early termination within exon 8. These cleft secondary palate 1 (csp1) mice have been backcrossed to FVB/NJ for at least 8 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ (Stock No. 001800) for at least one generation to establish the colony.
|Allele Name||cleft secondary palate 1|
|Allele Type||Chemically induced (ENU) (Hypomorph)|
|Allele Synonym(s)||line 27|
|Gene Symbol and Name||Prdm16, PR domain containing 16|
|Strain of Origin||BALB/c|
|General Note||The Ski gene has been excluded as a candidate gene for this mutation.|
|Molecular Note||This mutation was identified in an ENU mutagenesis screen. A cytosine to adenosine mutation is found within intron 6 at the base-pair position immediately preceding the invariant AG-dinucleotide splice acceptor site. The mutation causes variable skipping of exon 7. The consequence of this aberrant splicing event is a frame-shift leading to premature termination within exon 8 and inclusion of 46 out-of-frame amino acids. No shortened protein is detectable by western analysis, suggesting this mutant peptide is unstable. Full length RNA is detected and extended exposure of western blots of homozygous embryo head nuclear extracts detects protein indicating that this is a hypomorphic allele.|
|Mutations Made By|| |
David Beier, Harvard
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to FVB/NJ inbred mice (Stock No. 001800).
The donating investigator confirms perinatal lethality in all homozygotes due to cleft palate phenotype. The occurrence drops to 9% after backcrossing onto the C57BL/6J background for four generations, although 93% of these mice still die shortly after birth due to respiratory failure.
When using the cleft secondary palate 1, line 27 mouse strain in a publication, please cite the originating article(s) and include JAX stock #013100 in your Materials and Methods section.