SD-Mice - An Animal Model for Complex Anorectal Malformations*

Abstract

Animal models for morphological investigations of anorectal malformations are barely known to pediatric surgeons. In this study the morphological characteristics of a spontaneous mutation of the house mouse, the so-called SD-mouse, are described. The semidominant gene SD exerts its influence on the anorectum, the urogenital system and the axial skeleton. Many heterozygous (SD/+) and all homozygous (SD/SD) animals die shortly after birth due to their malformations. Surviving heterozygotes, identified by their short and deformed tails, may be used for breeding purposes. According to Mendel's laws, mating of such heterozygous yields 75% more or less malformed animals which may be used for morphological investigations. The morphological features of these animals were investigated in 61 neonatal SD-mice (33 SD/SD, 28 SD/+) and in 10 normal controls by microdissection and in 49 animals (25 SD/SD, 20 SD/+ and four normal controls) by serial sections. Of these, all homozygous and 10 heterozygous SD mice had anorectal malformations. The spectrum of these malformations is wide: very complex malformations in SD/SD mice and high anorectal malformations in SD/+ mice. These are comparable to morphological features found in humans and piglets. Hence the SD mouse represents an animal model for morphologic and embryonic investigations of complex anorectal malformations.

Anorectal Malformations Caused by Defects in Sonic Hedgehog Signaling

“…18 More recently, studies of Sd mice noted that the most consistent finding in this animal model was the loss of the dorsal cloaca and the presence of a short cloacal membrane. 16,56 In our anorectal mouse models, we found no evidence of active septation or lateral ridges formation/fusion on transverse sections of our mutant embryos, and similar to the Sd mice, we also observed a lack of formation of a normal dorsal cloaca. Our data now introduces a developmental model that furthers our understanding of anorectal malformation beyond the previous anatomical-based theories.…”

Animal models in pediatric surgery

“…These mice have an autosomal-dominant trait for imperforate anus and pass on this semi-dominant trait with high penetrance, where all of the homozygotes and most of the heterozygotes are affected. Kluth et al [83] looked at the spectrum of anorectal anomalies in this model and found that the pathological anatomical malformations in the heterozygous Sd mouse group were very similar to those seen in human neonates with anorectal anomalies as well as previous porcine models, which have been described. To date, the gene defective in Sd mice has yet to be identified.…”

Identification of the Modifier Locus that Suppresses Neonatal Lethality in (.FEMALE.DDD * .MALE.DH- Dh/+) F1-Dh/+ Male Mice

“…Several animal models for ARM are known. For example, Danforth's short tail (Sd) mouse is one of the oldest animal models for ARM [5]. The incidence of ARM is 36% in Sd/+ and 100% in Sd/Sd mice.…”