The genetics and morphology of two ‘luxoid’ mutants in the house mouse

Abstract

1. Dominant hemimelia (Dh) and postaxial hemimelia (px) both belong to the luxoid group of mouse mutants, tending to cause luxation of limb-bones associated with hemimelia and polydactyly or oligodactyly.2. Dh is about 4·8 units from leaden in linkage group XIII, while px is about 2·9 units from the microphthalmia locus in linkage group XI.3. The nature and range of skeletal anomalies found in Dh heterozygotes closely mimic those found in luxate heterozygotes and homozygotes. As in luxate, only the preaxial side of the hind-limb is affected, with (i) polydactyly or oligodactyly (sometimes also syndactyly), (ii) tibial hemimelia, (iii) reduction and fragmentation of the femur, (iv) reduction of the pubis. The more proximal the anomaly the less frequently does it occur; about 4% of Dh/ + mice show no limb anomaly. The defects in Dh homozygotes are similar but usually more extreme, with severe oligodactyly, loss of tibia, fragmentation of femur and reduction of pubis.4. All mice carrying Dh lack the spleen. Stomach size is reduced slightly in Dh/ + and greatly in Dh/Dh mice. In Dh/ + mice, the left kidney is either flattened antero-ventrally or (less frequently) hydropic; the right seems normal. Dh/Dh mice nearly always have severe hydronephrosis, as well as posterior visceral defects similar to those of the ‘uro-recto-caudal syndrome’. They usually die before weaning, but a few survive to maturity and a female has even bred.5. Preliminary developmental studies show that Dh/Dh skeletal defects can be traced back to the precartilaginous stage.6. When homozygous, px affects the postaxial side of the fore-limb and sometimes of the hind-limb also; a large ‘foramen infraspinatum’ is always present in the scapula. There may also be (i) oligodactyly and occasional syndactyly, (ii) ulnar hemimelia, (iii) distal reduction and distortion of the femur. Fore-limbs tend to be more severely affected on the right, but hind-limbs on the left. Extra sesamoid bones occur on the extensor side of digits in all four feet and are associated with extra tendons.7. Both sexes are sterile and show anomalies of the paramesonephric (Müllerian) ducts. In the female, the vagina is wholly or partly double and the uterine tubes uncoiled, with an abnormal relationship to the ovary. In the male the paramesonephric duct persists in the adult, while the vas deferens runs into the distal end of the vesicular gland instead of into the urethra. The epidermis of manus and pes shows abnormal dark papillae on the extensor side.8. The mean number of presacral vertebrae is reduced by 0·8 in Dh/ + and 1·6 in Dh/Dh mice. It is also reduced in high-grade postaxial hemimelics.9. The relationships of these two genes to other luxoid mutants are discussed.