Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: A murine model of Waardenburg syndrome variation

Journal Article · Sat Jun 15 00:00:00 EDT 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0289· OSTI ID:466675

Asher, Jr, J H; Harrison, R W; Morell, R; Carey, M L ^[1]

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1. Michigan State Univ., East Lansing, MI (United States); and others

Waardenburg syndrome type 1 is caused by mutations in PAX3. Over 50 human PAX3 mutations that lead to hearing, craniofacial, limb, and pigmentation anomalies have been identified. A PAX3 mutant allele, segregating in a family, can show reduced penetrance and variable expressivity that cannot be explained by the nature of the mutation alone. The Mus musculus Pax3 mutation Sp{sup d} (Splotch-delayed, Pax3{sup Sd}p), coisogenic on the C57BL/6J (B{sub 6}) genetic background, produces in heterozygotes a white belly spot with 100% penetrance and very few other anomalies. By contrast, many Sp{sup d}/+ BC{sub 1} progeny [F{sub 1} {female} Sp{sup d}/+ ({female} Sp{sup d}/+ B{sub 6} x {male} +/+ Mus spretus) x {male} +/+ B{sub 6}] exhibit highly variable craniofacial and pigmentary anomalies. Of the BC{sub 1} Sp{sup d}/+ progeny, 23.9% are estimated to be nonviable, and 32.1% are nonpenetrant for the white belly spot. The penetrance and expressivity of the Sp{sup d}/+ genotype are controlled in part by the genetic background and the sex of the individual. A minimum of two genes interact with Sp{sup d} to influence the craniofacial features of these mice. One of these genes may be either X-linked or sex-influenced, while the other is autosomal. The A-locus (Agouti) or a gene closely linked to A also plays a role in determining craniofacial features. At least one additional gene, possibly the A-locus or a gene linked to A, interacts with Sp{sup d} and determines the presence and size of the white belly spot. The viability of BC{sub 1} mice is influenced by at least three factors: Sp{sup d}, A-locus alleles or a gene closely linked to the A-locus, and the sex of the mouse. The BC{sub 1} mice provide an opportunity to identify genes that interact with and modify the expression of Pax3 and serve as a model to identify the genes that modify the expression of human PAX3 mutations. 65 refs., 3 figs., 6 tabs.

• OSTI ID: 466675
• Journal Information: Genomics, Vol. 34, Issue 3; Other Information: PBD: 15 Jun 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
PATIENTS
PHENOTYPE
SENSE ORGANS DISEASES
HEREDITARY DISEASES
GENOTYPE
GENETICS
BIOLOGICAL MODELS
GENES
DNA SEQUENCING
DNA-CLONING
GENE REGULATION
GENE MUTATIONS
MICE
HYBRIDIZATION
CONGENITAL MALFORMATIONS
PIGMENTS
DOMINANT MUTATIONS
ELECTROPHORESIS
POLYMERASE CHAIN REACTION