Previously, we discussed non-infectious diseases in rats. For a refresher, click here: [Maintaining Rat Colony Health: A Guide to Non-infectious Diseases in Rats]

In addition to factors related to routine husbandry practices, rats are also susceptible to various genetic diseases, known as congenital genetic abnormalities. Today, we will introduce some congenital genetic abnormalities commonly seen in rats.

Overview

The occurrence of genetic disorders is significantly influenced by mutagens and teratogens usage, but it also varies with strain, maternal age, health status, statistical coincidences, and human terminology.

Rats are susceptible to various genetic diseases, some of which make them valuable models, while others serve as confounding variables.

Renal Hydronephrosis

Renal hydronephrosis is a relatively common congenital defect in rats, characterized by the dilation of the renal pelvis on one or both sides.

While it may be inherited as a single dominant gene in Gunn rats, it appears to follow multi-gene (polygenic) inheritance in both Brown Norway rats (BN rats) and Sprague-Dawley rats (SD rats).

The right kidney is more commonly affected than the left. The severity of renal pelvic dilation varies, ranging from mild dilation to severe dilation, resulting in a translucent cystic appearance of the kidney. The ureters may also be affected to varying degrees.

However, it's important to note that pelvic dilation may occur in the normal renal pelvis of young animals, so caution is needed when identifying hydronephrosis.

Hydronephrosis can also be mistaken for pyelonephritis, since the dilated material of the renal pelvis is typically cloudy, and it may resemble polycystic kidneys or renal papillary necrosis. Culture and histopathology of the affected area can be used to differentiate these conditions.

Cardiac Defects

Congenital abnormalities of the cardiovascular system are less commonly reported in rats, but can include ventricular and atrial septal defects, defects of the right heart, valve, and endocardial cushion, as well as various abnormalities of large blood vessels.

In one group of Sprague-Dawley rats, the overall incidence of cardiac defects was estimated to be 2.3%.

Interestingly, in the Wistar-Kyoto inbred rat strain, which serves as a control for outbred spontaneously hypertensive rats (SHR), a higher rate of atrial septal defects leading to right ventricular hypertrophy has been observed.

Hydrocephalus and Epilepsy

Hydrocephalus is relatively rare and can be caused by congenital inheritance, occurring at a slightly higher proportion in small, isolated breeding populations. It is caused by the buildup of cerebrospinal fluid in the ventricles of the brain, and is often associated with the occurrence of unprovoked, recurring seizures, known as epilepsy.

Once hydrocephalus is confirmed, deliberate selective inbreeding can increase the occurrence rate in order to establish a population that can serve as an animal model for the disease. The resulting breeding population has an incidence rate of over 25% for hydrocephalus.

Epilepsy is common in people with various types of hydrocephalus. As such, rodent models of hydrocephalus which exhibit spontaneous seizures may also serve as models of epilepsy. Epilepsy has been reported in various mouse strains and breeds, but it is most frequently reported in various strains of Wistar rats. Wistar rats, in particular, have been used for studying audiogenic epilepsy.

Eye Defects

Congenital and genetic-based eye defects are quite common in certain rat strains.

Retinal degeneration is an age-related disease, and light exposure can accelerate its onset. In albino rats, the lack of pigment in the retinal pigment epithelial layer (RPEL) leads to increased retinal light exposure and may lead to further progression to retinal atrophy.

Corneal mineralization occurs in Fischer rats (F-344) with varying incidence rates ranging from 10% to 100%, depending on the sub-strains. It is characterized by calcium salt deposition along the interface between corneal epithelium and stroma, often visible as basophilic granules on conventionally stained sections via histopathological analysis.

Other ocular abnormalities reported in laboratory rats include retinal degeneration, cataracts, scleral ossification and chondrosis, as well as Optic Nerve Coloboma Spectrum of disc defect-related diseases.

Reproductive Tract Abnormalities

Several reproductive tract abnormalities have been reported in laboratory rats, including the vaginal septum in female Wistar and Sprague-Dawley rats.

If the uterine septum is completely intact in female rats, the affected rats are functionally infertile, as sperm cannot make contact with the eggs. If the uterine septum only partially obstructs sperm from entering the uterus, the affected rats have reduced reproductive capacity.

Androgen Insensitivity Syndrome, a.k.a. testicular feminization, is occasionally observed in rats and is more common in male pseudohermaphroditism. In these cases, the testes are present internally, but the external genitalia resemble female structures. Affected rats have XY chromosomes but express a default female phenotype.

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Reference:

[1]Fox J G, Anderson L C, Otto G, et al. Laboratory Animal Medicine:Third Edition[M]. 2015.

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