Genetic analyses of the vertebral anomalies of the IS strain of rat and the development of a BN congenic line with the anomalies

Abstract

SummaryIt is suggested that the anomalies in the IS rat are controlled by one or several genic factor(s) unrelated to LG I, II, IV, V, and VI and the LGs containing Amy-l and Cs-lloci.In the IS strain of rat (Rattus norvegicus), almost all individuals express singly or jointly several vertebral anomalies, mainly of the lumbar vertebrae. The anomalies include complete and incomplete unsegmentation, wedged and butterfly vertebrae, and result in scoliosis, kyphosis or both in about 50% of the rats. So, the IS strain is considered to be a spontaneous animal model of human congenital kyphoscoliosis (Ishibashi, 1979).In mice, many vertebral anomalies, including those of tail vertebrae, have been reported as monogenic or multifactoral traits (Kalter, 1978). In contrast, in the rat such defects are rarely reported. The following seem to comprise the known mutants: Chubby (cb), incisorless (in), Griineberg's lethal (lg), hypodactylyluxate (Ix), osteopetrosis (op), stubby (sb), stub (st), and toothless (tl) (Robinson, 1979). In the IS rats the anomalies are quite different morphologically from these gene effects in mouse and rat, and on the basis of preliminary experiments they seem to be controlled by 2 or more factors.We report here on the type, location, and degree of the vertebral anomalies in the IS strain, and on the results of a classical segregation analysis, involving crosses of the IS strain with inbred and partly inbred strains with normal vertebrae. We are developing a BN congenic line with the vertebral anomalies of the IS strain by repeated crossing and intercrossing. In this paper, we report the results to the N3F3 generation.

Genetical Studies of Low Plasma Alkaline Phosphatase (ALP) Activity in the IS Strain of Rats

“…Since in this study, we did not separated the plasma ALPs into bone, liver and intestinal ALPs, and also we did not measure phosphoethanolamine in the urine that is one of the diag-nostic findings of human hypophosphatasia [8], it is not certain whether the low plasma ALP activities in the IS rats are homologous with those in human hypophosphatasia or not. Now, we are developing a BN congenic line with the IS strain's vertebral anomalies [19]. By comparing the ALP activities of rats with and without vertebral anomalies in the congenic line, the relations between low ALP activity and vertebral anomaly will be clearly confirmed.…”

An N‐Ethyl‐N‐Nitrosourea (ENU) Mutagenized Mouse Model for Autosomal Dominant Nonsyndromic Kyphoscoliosis Due to Vertebral Fusion

“…Thus, the ISR model has similarities to HVF mice in having kyphosis, that is associated with segmentation defects affecting mainly the lumbar area, as well as narrowing of intervertebral spaces, irregularity of adjacent ends of vertebral bodies, and wedging and complete bony fusion of adjacent vertebral bodies 48, 49. However, the ISR model is suggested to have an autosomal recessive inheritance50 and although reduced expression of Hox10 and Hox11 have been reported,49 a mutation has not yet been identified. Details of body weight, lean mass, fat mass, and BMD content were not reported in the ISR model 48.…”

Progression of Congenital Kyphosis in Ishibashi Rats

“…Yamada et al (1982) suggested that the causal gene was a single autosomal recessive one with a penetrance of 50%. Clinico-biological studies disclosed a low level of serum alkaline phosphatase activity in ISR but this appeared unrelated to spinal malformations , Takahashi et al 1981.…”