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Abstract

Infantile hydrocephalus results in neurological deficits despite surgical treatment. Fetal-onset hydrocephalus in humans can be caused by developmental abnormalities that are genetic in origin. The H-Tx rat has hydrocephalus with 40% penetrance and a polygenic inheritance. A backcross with Fisher F344 inbred strain produced a total of 1500 progeny with 17.5% hydrocephalus. Of these, only 12.3% had overt disease and the remaining 5.2% had mild disease seen only after fixation of the brain. Disease severity was measured for all affected rats using the ratio of ventricle to brain width. The severity measure confirmed that there are two populations, mild hydrocephalus (M; ratio, <0.4) and severe hydrocephalus (S; ratio, >0.4), with a small overlap. For genotyping, the two populations were each subdivided based on the ratio measure to give a total of four groups of increasing severity. After an initial genome scan with microsatellite markers, all hydrocephalic rats and a subset of 128 normal progeny were genotyped on chromosomes 4, 9, 10, 11, 17 and 19. Rats in the mildest group had association with a locus on chromosome 4 (LOD 2.4), whereas those in the severest group were associated with a locus on chromosome 17 (LOD 3.2). All except the least affected group were associated with a heterozygous genotype on chromosomes 10 and 11 (LOD 4.5 and 3.5, respectively). Chromosomes 9 and 19 had weak linkage to hydrocephalus. The number of hydrocephalus-associated loci carried by each rat correlated with the severity of disease. It is concluded that the severity of hydrocephalus in H-Tx is influenced by different genetic loci.

The role of pericytic laminin in blood brain barrier integrity maintenance

“…1a,b. To investigate the severity of this phenotype, we measured ventricle-to-brain ratio, a parameter that positively correlates with ventricle size2728. Two distinct populations in PKO group were observed: one with ventricle-to-brain ratio comparable to the controls and one with larger ventricle-to-brain ratio (Fig.…”

“…It has been shown that the ventricle-to-brain ratio is linearly related to ventricle size and it provides a measurement of hydrocephalus severity2728. Thus, the ventricle-to-brain ratio was quantified and used to reflect the size of ventricles as described previously with minor modifications2728.…”

“…Thus, the ventricle-to-brain ratio was quantified and used to reflect the size of ventricles as described previously with minor modifications2728. Specifically, brains were subjected to sequential sectioning, and sections at the level of striatum and anterior commissure were selected for quantification.…”

Pathological characteristics of <i>Ccdc85c</i> knockout rats: a rat model of genetic hydrocephalus

“…These pathological characteristics are very similar to those of hhy mice [11]. hTX rats are known as a congenital hydrocephalus model [10], and hydrocephalus in hTX rats is caused by abnormal development of the subcommissural organ followed by closure of the cerebral aqueduct; however, the causative gene is unknown [8,9,22]. as a spontaneous cortical heterotopia model, telencephalic internal structural heterotopia (tish) rats have been reported [12].…”

Animal Models of Hydrocephalus

“…Despite these breakthroughs, the underlying genetic cause of this partially penetrant disorder is still unknown [96] [97] [98], which raises issues about its applicability. There is also concern that there are potential brain abnormalities in nonhydrocephalic "normal" H-Tx rats because they perform worse than Sprague-Dawley rats on behavioural tests [99].…”