Same as human and mouse, rat has five antibody isotypes (IgA, IgD, IgE, IgG, and IgM). For discussions on isotypes, subclasses, heavy chains, light chains, isotype compositions in different species, and constant and variable regions, please see Labome article on mouse antibody.

Figure 1. A rat.

The term 'rat' encompasses multiple species, more commonly and in this article, the species Norway rat (Rattus norvegicus), and black rat (Rattus rattus). Table 1 lists the Norway rat antibody classes, subclasses, gene names, and links to NCBI and IMGT gene databases. Table 2 lists the concentrations of the rat isotypes in serum under the usual or specific-pathogen-free (SPF)condition.

Table 3 shows the canonical protein sequence comparison between cognate mouse and rat IgG subclass constant region genes. Rat IgG2b constant region is most homologous to mouse IgG2a/b, and rat IgG1 and IgG2a constant regions are most homologous to mouse IgG1 constant regions [2], and rat IgG2c resembles mouse IgG3 [3, 4]. Such a high similarity between rat and mouse immunoglobulin constant regions requires considerations when secondary antibodies are used in double-labeling experiments or in cases where mouse antibodies are used in rat tissues or vice versa since antibodies against a rat or mouse immunoglobulin are likely to cross-react.

Labome antibody database organizes antibody products from over 100 high-quality suppliers. Many of them provide monoclonal antibodies generated from the rat. Table 4 lists a sample list of rat antibodies with different isotypes.

The common rat IgG isotype and subclasses have a molecular weight of 150 KD. Under the reducing condition, each heavy chain is about 50 KD, and each light chain is about 25 KD. See mouse antibody for an extensive discussion on immunoglobulin molecular weights.

Rat is one of the predominant animal hosts for monoclonal antibody production, second only to its rodent brethren, mouse. It is also an occasional host for polyclonal antibody generation. As of June 5, 2022, Labome antibody database lists 30337 rat monoclonal antibodies against 1485 human genes and 1472 mouse genes and a total of 510 genes from other species. One of the most commonly used rat monoclonal antibodies is the anti-mouse CD45 (clone 30-F11) antibody; its myriad of fluorophore-conjugated variants are commonly used in flow cytometry for the identification of immune cells. Other examples include commonly used neuronal marker: rat anti-somatostatin clone YC7 [223] ; integrin antibodies like integrin αV antibody 12-0512-82 and integrin β1 antibody 12-0181-82 from Thermo Fisher and integrin α5 antibody 103805 from BioLegend [224] ; HA antibodies like Roche 11867423001 [225].

Different rat strains have been used to generate monoclonal antibodies. Both outbred strains Wistar [226, 227] and Sprague-Dawley [228, 229], especially the inbred Lou/C strain [230, 231], which is derived from Wistar strain, are commonly used for antibody immunization. Lou/C strain possesses the advantage that the widely used IR983F myeloma for hybridoma fusion is of Lou origin. Simons IM et al generated a highly specific rat monoclonal antibody against GABARAP, a crucial protein involved in autophagy, through injecting purified full-length GST-fused GABARAP protein into Lou/C rats and fusing the immune spleen cells with mouse myeloma cell line P3X63-Ag8.653 [230].

Labome surveys literature to develop Validated Antibody Database. Table 5 lists some of the most commonly cited rat monoclonal antibodies among the articles Labome has curated.

When an antibody originated from a rat is used on rat tissue, it is essential to consider the endogenous immunoglobulin and Fc receptor, which can bind to secondary antibodies. There are several approaches to help with the detection of primary antibody binding. The same principles here also apply to the situations where mouse antibodies are used on mouse tissues.

The approaches are:

1. directly label the primary antibody with a fluorophore, or biotinylate the primary antibody and then detect any signal with biotin-streptavidin system;
2. block the endogenous immunoglobulin with anti-rat IgG Fab, for example, Fab goat anti-rat IgG. Since Fab fragment cannot be picked up by the secondary antibodies, the endogenous IgG is masked;
3. block the non-specific binding with 5% serum from the species where the secondary antibody was raised.

Rat is also a widely used research model, and many antibodies against rat genes are available. As of June 5, 2022, Labome antibody database lists 73573 monoclonal antibodies against 8084 rat genes, among which at least 2401 are recombinant antibodies against 1609 rat genes (see a summary of antibodies against rat genes).