Pre‐B lymphomas in SL/Kh mice: A multifactorial disease model

Abstract

The pre-B lymphoma in the inbred mouse strain SL/Kh is an excellent multifactorial disease model. The endogenous murine leukemia virus provirus Emv11, genetically acquired from an AKR progenitor, is the pathogenetic agent that reintegrates to dysregulate several host genes, i. pontaneous pre-B lymphoma is a relatively rare category among mouse lymphoid neoplasias. 1) We have established the SL/Kh strain mice, which has an extremely high incidence of pre-B lymphomas with short latency induced by endogenous murine leukemia virus (MuLV).2, 3) Studies on SL/Kh mice for a quarter of century have revealed that they provide an excellent multifactorial disease model. In this article, we will review the origin of the SL/Kh strain, the pathology, virology, and molecular mechanism of lymphomagenesis, the genetic and epigenetic determination of types, and the latency of diseases.

Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas

“…So far, retroviral integrations at Ebfaz have only been identified in AKXD27 lymphomas, although, to date, this is the only AKXD strain examined for Ebfaz integrations so it remains possible that Ebfaz integrations will be found in other AKXD strain tumors as well. Interestingly, in the SL/Kh mouse model for pre-B lymphomas, Evi3 is the most frequent site of retroviral integration (75% of tumors) (Hiai et al, 2003). It will be interesting to determine whether SL/Kh lymphomas also contain retroviral integrations at Ebfaz.…”

Hotspots of MLV integration in the hematopoietic tumor genome

“…This strain possesses pathogenic endogenous ecotropic murine virus 11 ( Emv11 ) that has been mapped onto chromosome 7 and is shared with the AKR mouse strain. 23, 32 In the SL/Kh strain, the pro- to pre-B cells in the bone marrow expand 28, 33 and newly acquire more than one copy of the proviral genome during the process of lymphomagenesis; 34 >90% of these mice spontaneously develop sIgM- pro- or pre-B lymphomas that are positive for BP-1 by the age of 6 months. 28, 32 Notably, the phenotypic stability and the tumor incidence are significantly higher than those in other models, BXH2 24 and AKXD.…”

“…43 Notably, several integration sites were shared by different tumors of this strain. 32, 41, 43 In particular, a 170 bp segment within the second intron was found to be the hotspot for MLV integration (Figure 3). Furthermore, within this region, several nucleotides were shared by different pre-B-cell tumors.…”

“…45, 55 We also reported that this gene is the most frequent integration site as well in pre-B-cell lymphoma in SL/Kh mice. 32 The encoded ZFP521 regulates and activates pre-B-cell receptor signal pathways. 45 …”

“…32 Specifically, the integration sites in the genome of pre-B-cell tumors in SL/Kh mice (p, q, r, s, t) are shown in Figure 4. The integration occurred once or twice within a 50 bp segment located in the region of the second to the third exon of Zfp521 in the pre-B-cell lymphoma genome during the lifetime of the mouse.…”